Brain related PBM Research

Long-Term Near-Infrared Photobiomodulation for Anxious Depression Complicated by Takotsubo Cardiomyopathy.

Caldieraro MA, Sani G, Bui E, Cassano P

Department of Psychiatry Massachusetts General Hospital Boston, MA and Serviço de PsiquiatriaHospital de Clínicas de Porto Alegre Rua Ramiro Barcelos Porto Alegre, Brazil Departments of Neurosciences, Mental Health, and Sensory Organs Sapienza University Rome, Italy and Faculty of Medicine and Psychology and Unit of PsychiatrySant’Andrea Hospital Via di Grottarossa Rome, Italy Depression Clinical and Research Program Department of PsychiatryMassachusetts General Hospital Boston, MA and Center for Anxiety and Traumatic Stress Disorders Department of Psychiatry Massachusetts General Hospital Boston, MA Depression Clinical and Research Program Department of Psychiatry Massachusetts General Hospital Boston, MA and Center for Anxiety and Traumatic Stress Disorders Department of Psychiatry Massachusetts General Hospital Boston, MApcassano@mgh.harvard.edu..

J Clin Psychopharmacol 2018 Mar 29

https://www.ncbi.nlm.nih.gov/pubmed/?term=29601319

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Transcranial near-infrared laser therapy in improving cognitive recovery of function following traumatic brain injury

Yao X, Liu C, Feng D, Yin J, Chen G

Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China Scott & White Clinic-Temple, 2401 S.31st Street, Temple, TX76508, USA Department of Neurosurgery, Taixing Chinese Medicine Hospital, Taixing 225400, China Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.

Traumatic brain injury (TBI) is turned into a major health and socioeconomic problem affecting young people and military personnel. Numerous TBI patients experienced the sequela of brain injury called cognitive impairment, which reduced functions in attention, working memory, motivation, and execution. In recent years, transcranial near-infrared laser therapy (tNiRLT) as a possible therapy gradually applied in treating cognitive impairment post-TBI. In the present review, the biological mechanisms of transcranial tNiRLT for TBI are synthesized mainly based on the photonic impact to chronic mild TBI. Various exciting molecular events possibly occur during the procedure, such as stimulation of ATP production, regional cerebral blood flow, acupoint, neurogenesis and synaptogenesis, reduction of anti-inflammatory also existed. Some animal experiments and clinical studies of tNiRLT for TBI are outlined. Several labs have displayed that tNiRLT is effective not only improving neurological functions but also increasing memory and learning capacity in rodent animals' model of TBI. In a 2 patients case report and a 11-case series, cognitive functions were ameliorated. Efficacy on cognitive and emotional effects was also observed in a double-blind, controlled clinical study. Several Randomized, parallel, double blinds, sham controlled trials are underway, aiming to evaluating the efficacy of tLED on cognitive functions and neuropsychiatric status in participants post-TBI. Therefore, tNiRLT is a promising method applied to cognitive impairment following TBI.

Curr Neuropharmacol 2018 04 13

https://www.ncbi.nlm.nih.gov/pubmed/?term=29564977

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Nano Pulsed Laser Therapy Is Neuroprotective In A Rat Model Of Blast-Induced Neurotrauma.

Esenaliev RO, Petrov IY, Petrov Y, Guptarak J, Boone DR, Mocciaro E, Weisz H, Parsley MO, Sell SL, Hellmich HL, Ford JM, Pogue C, DeWitt D, Prough DS, Micci MA

University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States. The University of Texas Medical Branch, Neuroscience and Cell Biology, Galveston, Texas, United States. University of Texas Medical Branch, Center for Biomedical Engineering, Galveston, Texas, United States ; riesenal@utmb.edu. University of Texas Medical Branch, Center for Biomedical Engineering, Galveston, Texas, United States ; irpetrov@utmb.edu. University of Texas Medical Branch, Center for Biomedical Engineering, Galveston, Texas, United States ; YYpetrov@utmb.edu. University of Texas Medical Branch, Biochemistry and Molecular Biology, Galveston, Texas, United States ; juguptat@UTMB.EDU. University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; drkenned@utmb.edu. University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; emmoccia@utmb.edu. The University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; haweisz@utmb.edu. University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; maparsle@utmb.edu. University of Texas Medical Branch, Anesthesiology , 301 University Blvd , Galveston, Texas, United States , 77555-1102 ; slsell@utmb.edu. University of Texas Medical Branch, Anesthesiology , 601 Harborside Drive , Bldg 21, Rm 3.202H , Galveston, Texas, United States , 77555-1102 ; hhellmic@utmb.edu. The University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; joford@utmb.edu. The University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; connorpogue@sbcglobal.net. University of Texas Medical Branch, Anesthesiology, Galveston, Texas, United States ; ddewitt@utmb.edu. The University of Texas Medical Branch, Anesthesiology , 301 University Blvd. , Galveston, Texas, United States , 77555-0591. 2602 Avenue OGalvston, Texas, United States , 77550 ; dsprough@utmb.edu. University of Texas Medical Branch, Anesthesiology , 301 University Blvd , Galveston, Texas, United States , 77555 ; mmicci@utmb.edu..

We have developed a novel, non-invasive Nano-Pulsed Laser Therapy (NPLT) system that combines the benefits of near-infrared laser light (808 nm) and ultrasound (optoacoustic) waves, which are generated with each short laser pulse within the tissue. We tested NPLT in a rat model of blast-induced neurotrauma to determine whether transcranial application of NPLT provides neuroprotective effects. The laser pulses were applied on the intact rat head one hour after injury using a specially developed fiber-optic system. Vestibulomotor function was assessed on post-injury days (PIDs) 1-3 on the beam balance and beam walking tasks. Cognitive function was assessed on PIDs 6-10 using a working memory Morris water maze test. BDNF and caspase-3 mRNA expression was measured by qRT-PCR in laser-captured cortical neurons. Microglia activation and neuronal injury were assessed in brain sections by immunofluorescence using specific antibodies against CD68 and active caspase-3, respectively. In the vestibulomotor and cognitive (Morris water maze) tests, NPLT-treated animals performed significantly better than the untreated blast group and similarly to sham animals. NPLT up-regulated mRNA encoding BDNF and down-regulated the pro-apoptotic protein caspase-3 in cortical neurons. Immunofluorescence demonstrated that NPLT inhibited microglia activation and reduced the number of cortical neurons expressing activated caspase-3. NPLT also increased expression of BDNF in the hippocampus and the number of proliferating progenitor cells in the dentate gyrus. Our data demonstrate a neuroprotective effect of NPLT and prompt further studies aimed to develop NPLT as a therapeutic intervention after TBI.

J Neurotrauma 2018 Mar 21

https://www.ncbi.nlm.nih.gov/pubmed/?term=29562823

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Learning from clinical phenotypes: Low-dose biophotonics therapies in oral diseases.

Rahman SU Mosca RC Govindool Reddy S Nunez SC Andreana S Mang TS Arany PR

Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA. Energetic and Nuclear Research Institute, Radiation Technology Center, São Paulo, Brazil. Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA. Biomedical Engineering and Bioengineering, Universidade Brasil, São Paulo, Brazil. Restorative and Implant Dentistry, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA. Oral and Maxillofacial Surgery, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA. Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA..

This narrative review on the use of biophotonics therapies for management of oral diseases is written as a tribute to Prof. Crispian Scully. His seminal contributions to the field are highlighted by the detailed, comprehensive description of clinical presentations of oral diseases. This has enabled a more thorough, fundamental understanding of many of these pathologies by research from his group as well as inspired mechanistic investigations in many groups globally. In the same vein, a major emphasis of this narrative review is to focus on the evidence from human case reports rather than in vitro or in vivo animal studies that showcases the growing and broad impact of biophotonics therapies. The similarities and differences between two distinct forms of low-dose biophotonics treatments namely photodynamic therapy and photobiomodulation therapy are discussed. As evident in this review, a majority of these reports provide promising evidence for their clinical efficacy. However, a lack of adequate technical details, precise biological rationale, and limited outcome measures limits the current utility of these treatments. Future investigations should attempt to address these shortcomings and develop better designed, rigorous, controlled studies to fully harness the tremendous potential of low-dose biophotonics therapies.

Oral Dis 2018 Mar

https://www.ncbi.nlm.nih.gov/pubmed/?term=29480614

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[Three-month rehabilitation of a patient with the III, IV and VI cranial nerve damage caused by a neurosurgery of the left internal carotid artery aneurysm].

Mosi ski E Kikowski Irzma ski R

Klinika Chorób Wewn trznych i Rehabilitacji Kardiologicznej, Wydzia Wojskowo-Lekarski, Uniwersytet Medyczny w odzi, ód , Polska. O rodek Profilaktyki i Rehabilitacji Creator Sp. z o.o. w odzi, ód , Polska. Klinika Chorób Wewn trznych i Rehabilitacji Kardiologicznej, Wydzia Wojskowo-Lekarski, Uniwersytet Medyczny w odzi, ód , Polska..

OBJECTIVE: Introduction: Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. Third nerve damage weakens the muscles innervated by the nerve . Also adversely affect the fourth and sixth nerve , causing impairment of their activity. Rehabilitation third nerve palsy is rarely described in the available literature . The whole process is very difficult , but the effects of physiotherapy is very beneficial for the patient. The aim:The assessment of the influence of the outpatient rehabilitation on the patient’s condition after a three-month treatment and the use of physical therapy. PATIENTS AND METHODS: Material and methods:Case studies of the 38-yerar-old patient after having operated a big aneurism of the left ICA, which was clipped. After the procedure, the III, IV and VI cranial nerves were deeply impaired and the amnesic aphasia occurred. The patient started the rehabilitation a month after the incident. To assess the process of rehabilitation, the own movement examination of the eyeball was implemented. Active and passive exercises, Tigger Point therapy, kinesiotaping, laser and electrostimulation were inserted. RESULTS: Results: The significant improvement of the eyeball movement has been proved on the basis of the same own examination. A physiotherapy has had a positive influence on the speech disorder, namely amnesic aphasia, and after the month of the rehabilitation it has been completely removed. The positive influence of the rehabilitation, which has been pointed out, is clinically essential. CONCLUSION: Conclusions: Obtained results have not been described in literature yet, that is why it is essential to widen further research and emphasise the importance of the rehabilitation, which is rarely implemented in an intense way in such medical conditions.

Wiad Lek 2017

https://www.ncbi.nlm.nih.gov/pubmed/?term=29478991

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Evidence for encephalopsin immunoreactivity in interneurones and striosomes of the monkey striatum.

El Massri N Cullen KM Stefani S Moro C Torres N Benabid AL Mitrofanis J

Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. john.mitrofanis@sydney.edu.au..

In this study, we examined the cellular distribution of encephalopsin (opsin 3; OPN3) expression in the striatum of non-human primates. In addition, because of our long standing interest in Parkinson’s disease and neuroprotection, we examined whether parkinsonian (MPTP; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) insult and/or photobiomodulation (670 nm) had any impact on encephalopsin expression in this key area of the basal ganglia. Striatal sections of control naïve monkeys, together with those that were either MPTP- and/or photobiomodulation-treated were processed for immunohistochemistry. Our results revealed two populations of striatal interneurones that expressed encephalopsin, one of which was the giant, choline acetyltransferase-containing, cholinergic interneurones. The other population had smaller somata and was not cholinergic. Neither cell group expressed the calcium-binding protein, parvalbumin. There was also rich encephalopsin expression in a set of terminals forming striosome-like patches across the striatum. Finally, we found that neither parkinsonian (MPTP) insult nor photobiomodulation had any effect on encephalopsin expression in the striatum. In summary, our results revealed an extensive network of encephalopsin containing structures throughout the striatum, indicating that external light is in a position to influence a range of striatal activities at both the interneurone and striosome level.

Exp Brain Res 2018 Jan 29

https://www.ncbi.nlm.nih.gov/pubmed/?term=29379995

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Brain Photobiomodulation Therapy: a Narrative Review.

Salehpour F Mahmoudi J Kamari F Sadigh-Eteghad S Rasta SH Hamblin MR

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. farzadsalehpour1988@gmail.com. Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran. farzadsalehpour1988@gmail.com. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran. Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz, Iran. School of Medical Sciences, University of Aberdeen, Aberdeen, UK. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA. hamblin@helix.mgh.harvard.edu. Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. hamblin@helix.mgh.harvard.edu. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA. hamblin@helix.mgh.harvard.edu..

Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson’s disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.

Mol Neurobiol 2018 Jan 11

https://www.ncbi.nlm.nih.gov/pubmed/?term=29327206

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Photobiomodulation using low-level laser therapy (LLLT) for patients with chronic traumatic brain injury: a randomized controlled trial study protocol.

Poiani GDCR Zaninotto AL Carneiro AMC Zangaro RA Salgado ASI Parreira RB de Andrade AF Teixeira MJ Paiva WS

Division of Neurosurgery, University of Sao Paulo Medical School, Av. Dr. Arnaldo, 455 – Cerqueira César, 01246-903, Sao Paulo, SP, Brazil. comporta.saude@gmail.com. Division of Psychology at Hospital of Clinics, University of Sao Paulo Medical School, Sao Paulo, Brazil. Division of Neurosurgery, University of Sao Paulo Medical School, Av. Dr. Arnaldo, 455 – Cerqueira César, 01246-903, Sao Paulo, SP, Brazil. Institute of Biomedical Engineering, Anhembi Morumbi University, Sao Jose dos Campos, Sao Paulo, Brazil. Institute of Biomedical Engineering, Anhembi Morumbi University, Sao Jose dos Campos, Sao Paulo, Brazil. Center for Innovation, Technology and Education – CTE, Sao Jose dos Campos, Sao Paulo, Brazil. Salgado Institute of Integral Health; School of Postural and Manual Therapy, Londrina, Parana, Brazil. Salgado Institute of Integral Health; School of Postural and Manual Therapy, Londrina, Parana, Brazil. Division of Neurosurgery, University of Sao Paulo Medical School, Av. Dr. Arnaldo, 455 – Cerqueira César, 01246-903, Sao Paulo, SP, Brazil. Division of Neurosurgery, University of Sao Paulo Medical School, Av. Dr. Arnaldo, 455 – Cerqueira César, 01246-903, Sao Paulo, SP, Brazil. Division of Neurosurgery, University of Sao Paulo Medical School, Av. Dr. Arnaldo, 455 – Cerqueira César, 01246-903, Sao Paulo, SP, Brazil..

BACKGROUND: Photobiomodulation using low-level laser therapy (LLLT) has been tested as a new technique to optimize recovery of patients with traumatic brain injury (TBI). The aim of this study is to evaluate inhibitory attentional control after 18 sessions of active LLLT and compare with the placebo group (sham LLLT). Our exploratory analysis will evaluate the efficacy of the active LLLT on verbal and visuospatial episodic memory, executive functions (working memory, verbal and visuospatial fluency, attentional processes), and anxiety and depressive symptoms compared to the sham group. METHODS/DESIGN: A randomized double-blinded trial will be made in 36 patients with moderate and severe TBI. The active LLLT will use an optical device composed of LEDs emitting 632 nm of radiation at the site with full potency of 830 mW. The cranial region with an area of 400 cm2 will be irradiated for 30 min, giving a total dose per session of 3.74 J/cm2. The sham LLLT group contains only an LED device with power < 1 mW, only serving to simulate the irradiation. Each patient will be irradiated three times per week for six weeks, totaling 18 sessions. Neuropsychological assessments will be held one week before the beginning of the sessions, after one week, and three months after the end of LLLT sessions. Memory domain, attention, executive functioning, and visual construction will be evaluated, in addition to symptoms of depression, anxiety, and social demographics. DISCUSSION: LLLT has been demonstrated as a safe and effective technique in significantly improving the memory, attention, and mood performance in healthy and neurologic patients. We expect that our trial can complement previous finds, as an effective low-cost therapy to improve cognitive sequel after TBI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393079 . Registered on 20 February 2015.

Trials 2018 Jan 08

https://www.ncbi.nlm.nih.gov/pubmed/?term=29310710

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Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice.

Salehpour F Farajdokht F Erfani M Sadigh-Eteghad S Shotorbani SS Hamblin MR Karimi P Rasta SH Mahmoudi J

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran; Higher Academic Education Institute of Rab-Rashid, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115, United States; Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, United States. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz, Iran; School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: Mahmoudi2044@yahoo.com..

Sleep deprivation (SD) causes oxidative stress in the hippocampus and subsequent memory impairment. In this study, the effect of near-infrared (NIR) photobiomodulation (PBM) on learning and memory impairment induced by acute SD was investigated. The mice were subjected to an acute SD protocol for 72 hr. Simultaneously, NIR PBM using a laser at 810 nm was delivered (once a day for 3 days) transcranially to the head to affect the entire brain of mice. The Barnes maze and the What-Where-Which task were used to assess spatial and episodic-like memories. The hippocampal levels of antioxidant enzymes and oxidative stress biomarkers were evaluated. The results showed that NIR PBM prevented cognitive impairment induced by SD. Moreover, NIR PBM therapy enhanced the antioxidant status and increased mitochondrial activity in the hippocampus of SD mice. Our findings revealed that hippocampus-related mitochondrial damage and extensive oxidative stress contribute to the occurrence of memory impairment. In contrast, NIR PBM reduced hippocampal oxidative damage, supporting the ability of 810 nm laser light to improve the antioxidant defense system and maintain mitochondrial survival. This confirms that non-invasive transcranial NIR PBM therapy ameliorates hippocampal dysfunction, which is reflected in enhanced memory function.

Brain Res 2018 Jan 04

https://www.ncbi.nlm.nih.gov/pubmed/?term=29307593

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Laser acupuncture treatment of neuropathic pain in a boy with brain tumour.

Butkovic D, Tot OK

University of Osijek Medical School, Croatia; Children’s Hospital Zagreb, Paediatric Pain Clinic, Croatia. Electronic address: diana.butkovic1@gmail.com. University of Osijek Medical School, Croatia; Clinical Hospital Centre Osijek, Department for Pain Therapy, Croatia..

Neuropathic pain occurrence is associated with some cytostatic and antibiotics use. Pharmacological therapy for the treatment of neuropathic pain is sometimes unsuccessful, and complementary methods like acupuncture are included. In this case report, a 14-year-old boy with cerebral tumour and neuropathic pain in his feet after chemotherapy and linezolid use is presented. A complete cessation of neuropathic pain symptoms like hyperalgesia and allodynia was accomplished after laser acupuncture application.

Complement Ther Med 2017 Dec

https://www.ncbi.nlm.nih.gov/pubmed/?term=29154067

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Photobiomodulation for Traumatic Brain Injury and Stroke.

Hamblin MR,

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA. Department of Dermatology, Harvard Medical School, Boston, MA. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA..

There is a notable lack of therapeutic alternatives for what is fast becoming a global epidemic of traumatic brain injury (TBI). Photobiomodulation (PBM) employs red or near-infrared (NIR) light (600-1100nm) to stimulate healing, protect tissue from dying, increase mitochondrial function, improve blood flow, and tissue oxygenation. PBM can also act to reduce swelling, increase antioxidants, decrease inflammation, protect against apoptosis, and modulate microglial activation state. All these mechanisms of action strongly suggest that PBM delivered to the head should be beneficial in cases of both acute and chronic TBI. Most reports have used NIR light either from lasers or from light-emitting diodes (LEDs). Many studies in small animal models of acute TBI have found positive effects on neurological function, learning and memory, and reduced inflammation and cell death in the brain. There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis. In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function. Clinical studies have been conducted in patients suffering from the chronic effects of TBI. There have been reports showing improvement in executive function, working memory, and sleep. Functional magnetic resonance imaging has shown modulation of activation in intrinsic brain networks likely to be damaged in TBI (default mode network and salience network).

J Neurosci Res 2017 Nov 13

https://www.ncbi.nlm.nih.gov/pubmed/?term=29131369

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Near infrared light decreases synaptic vulnerability to amyloid beta oligomers.

Comerota MM, Krishnan B, Taglialatela G

Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA. mmcomero@utmb.edu. Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA. bakrishn@utmb.edu. Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA. gtaglial@utmb.edu..

Synaptic dysfunction due to the disrupting binding of amyloid beta (A ) and tau oligomers is one of the earliest impairments in Alzheimer’s Disease (AD), driving initial cognitive deficits and clinical manifestation. Consequently, there is ample consensus that preventing early synaptic dysfunction would be an effective therapeutic strategy for AD. With this goal in mind, we investigated the effect of a treatment of mice with near infrared (NIR) light on synaptic vulnerability to A oligomers. We found that A oligomer binding to CNS synaptosomes isolated from wild type (wt) mice treated with NIR light was significantly reduced and the resulting suppression of long term potentiation (LTP) by A oligomers was prevented. Similarly, APP transgenic mice treated with NIR showed a significant reduction of endogenous A at CNS synapses. We further found that these phenomena were accompanied by increased synaptic mitochondrial membrane potential in both wt and Tg2576 mice. This study provides evidence that NIR light can effectively reduce synaptic vulnerability to damaging A oligomers, thus furthering NIR light therapy as a viable treatment for AD.

Sci Rep 2017 Nov 08

https://www.ncbi.nlm.nih.gov/pubmed/?term=29118388

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Laser Acupuncture at GV20 Improves Brain Damage and Oxidative Stress in Animal Model of Focal Ischemic Stroke.

Jittiwat J

Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand; Integrative Complimentary Alternative Medicine Research and Development Group, Khon Kaen University, Khon Kaen, Thailand. Electronic address: jinatta@gmail.com..

The burden of stroke is high and is continually increasing due to a dramatic growth in the world’s elderly population. Novel therapeutic strategies are therefore required. The present study sought to determine the effect of laser acupuncture at GV20 on brain damage, oxidative-status markers in the cerebral cortex, and superoxide dismutase in the mitochondria of an animal model of focal ischemic stroke. Wistar rats, weighing 300-350 g, were divided into the following four groups: (1) control; (2) permanent occlusion of the right middle cerebral artery (Rt.MCAO) alone; (3) Rt.MCAO plus sham laser acupuncture; and (4) Rt.MCAO plus laser-acupuncture groups. Sham laser acupuncture or laser acupuncture was performed once daily at the GV20 (Baihui) acupoint for 14 days following Rt.MCAO. Half of the rats in each group were examined by 2,3,5-triphenyltetrazolium chloride staining to determine the brain infarct volume, while the other half were examined by biochemical assays to determine the malondialdehyde level, and the glutathione peroxidase, catalase, and superoxide-dismutase activities in the brain-cortex mitochondria. The results showed that laser acupuncture at GV20 significantly decreased the brain infarct volume and malondialdehyde level, and increased the catalase, glutathione peroxidase, and superoxide-dismutase activities in cerebral ischemic rats. In conclusion, laser acupuncture at GV20 decreases the brain infarct volume in cerebral ischemic rats, at least in part due to decreased oxidative stress. Further study is warranted to investigate other possible underlying mechanisms.

J Acupunct Meridian Stud 2017 Oct

https://www.ncbi.nlm.nih.gov/pubmed/?term=29078967

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Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells.

Yang L, Tucker D, Dong Y, Wu C, Lu Y, Li Y, Zhang J, Liu TC, Zhang Q

Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science, South China Normal University, Guangzhou, China; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.Electronic address: qzhang@augusta.edu..

Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm(2), total 294J at scalp level) was applied on the infarct injury area (1.8mm anterior to the bregma and 2.5mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.

Exp Neurol 2017 Oct 19

https://www.ncbi.nlm.nih.gov/pubmed/?term=29056360

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Multi-Watt Near-Infrared Phototherapy for the Treatment of Comorbid Depression: An Open-Label Single-Arm Study.

Henderson TA, Morries LD

Neuro-Laser Foundation, Centennial, CO, United States. The Synaptic Space Inc., Centennial, CO, United States. Neuro-Luminance Inc., Centennial, CO, United States. Dr. Theodore Henderson, Inc., Centennial, CO, United States. Neuro-Laser Foundation, Centennial, CO, United States..

BACKGROUND: The treatment of depression has been hampered by low efficacy of antidepressant medications and safety concerns with alternative modalities. Recent work demonstrated that multi-Watt transcranial near-infrared light therapy (NILT) can effectively treat traumatic brain injury (TBI). The current objective is to explore multi-Watt NILT efficacy in a proof-of-concept study as a treatment for depression. METHODS: Thirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton depression rating scale. Each completed the Quick Inventory of Depression Symptomatology-Self Report (QIDS) before and after treatment. Patients received multi-Watt NILT using near-infrared lasers (810/980 nm at 8-15 W) applied to forehead and temporal regions bilaterally for 9-12 min to each area. Pre- and posttreatment scores were analyzed by paired t-tests. RESULTS: All met QIDS criteria for mild to severe depression and 69% had prior antidepressant trials. For 36 of the 39 patients, after 16.82 ± 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by ≥50%). For 32 of 39 patients, posttreatment QIDS scores indicated a remission from depression (decrease of QIDS total score ≤5). Overall, the QIDS score fell from 14.10 ± 3.39 to 3.41 ± 3.30 SD (p = 6.29 10(-19)). With 12 or fewer treatments, QIDS score dropped from 14.83 ± 2.55 to 4.17 ± 3.93. Patients receiving ≥13 treatments showed a change in QIDS score from 13.67 ± 3.64 to 3.11 ± 3.14. Those (N = 15) who received the entire treatment course within ≤8 weeks (5.33 ± 1.72 weeks) showed a change in QIDS score from 13.86 ± 3.14 to 4.5 ± 3.94. Suicidal ideation resolved in all, but two patients. Patients remained in remission for up to 55 months after a single course of treatment. CONCLUSION: This is the first report of high-powered NILT showing efficacy for depression. Multi-Watt NILT showed far greater efficacy and persistent benefit compared to low-power (<1 Watt) infrared light treatments. Patients saw benefit often within four treatments and resolution of depressive symptoms occurred within 4 weeks for some. These data raise an intriguing possibility-that multi-Watt NILT may be a safe, effective, and rapid treatment for depression comorbid with TBI and possibly primary major depression disorder. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.

Front Psychiatry 2017

https://www.ncbi.nlm.nih.gov/pubmed/?term=29033859

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Impact of heat on metabolic and hemodynamic changes in transcranial infrared laser stimulation measured by broadband near-infrared spectroscopy.

Wang X, Reddy DD Nalawade SS Pal S Gonzalez-Lima F Liu H

University of Texas at Arlington, Department of Bioengineering, Arlington, Texas, United States. University of Texas at Arlington, Department of Mathematics, Arlington, Texas, United States. University of Texas at Austin, Department of Psychology and Institute for Neuroscience, Austin, Texas, United States. University of Texas at Arlington, Department of Bioengineering, Arlington, Texas, United States..

Transcranial infrared laser stimulation (TILS) has shown effectiveness in improving human cognition and was investigated using broadband near-infrared spectroscopy (bb-NIRS) in our previous study, but the effect of laser heating on the actual bb-NIRS measurements was not investigated. To address this potential confounding factor, 11 human participants were studied. First, we measured time-dependent temperature increases on forehead skin using clinical-grade thermometers following the TILS experimental protocol used in our previous study. Second, a subject-averaged, time-dependent temperature alteration curve was obtained, based on which a heat generator was controlled to induce the same temperature increase at the same forehead location that TILS was delivered on each participant. Third, the same bb-NIRS system was employed to monitor hemodynamic and metabolic changes of forehead tissue near the thermal stimulation site before, during, and after the heat stimulation. The results showed that cytochrome-c-oxidase of forehead tissue was not significantly modified by this heat stimulation. Significant differences in oxyhemoglobin, total hemoglobin, and differential hemoglobin concentrations were observed during the heat stimulation period versus the laser stimulation. The study demonstrated a transient hemodynamic effect of heat-based stimulation distinct to that of TILS. We concluded that the observed effects of TILS on cerebral hemodynamics and metabolism are not induced by heating the skin.

Neurophotonics 2018 Jan

https://www.ncbi.nlm.nih.gov/pubmed/?term=28948191

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Treatment of Depression: A Systematic Review

Swedish Council on Health Technology Assessment

Stockholm.

Conclusions: Treatment of depression should aim at full recovery, i.e., that the patient is not only symptom free but also able to fully function socially and at work. That objective can be achieved for the great majority of patients if available treatment options are consistently exploited (strong scientific evidence). There are a large number of antidepressants and several types of psychotherapy that have been shown to be effective for treating major depression in adults (strong scientific evidence). For the acute treatment of mild or moderate depression in adults, several types of psychotherapy are as effective as tricyclic antidepressants (TCAs) (strong scientific evidence) and probably as effective as selective serotonin reuptake inhibitors (SSRIs) (moderately strong scientific evidence). Antidepressants and electroconvulsive therapy (ECT) have proven to be most effective for severe depression, such as melancholia and psychotic depression (moderately strong scientific evidence). Antidepressants and ECT produce more rapid results than psychotherapy (moderately strong scientific evidence). Maintenance psychotherapy reduces or delays relapses, particularly in cases where acute antidepressant treatment or psychotherapy has not rendered the patient symptom free (strong scientific evidence). No significant differences have emerged in the effectiveness of various antidepressants for the treatment of mild and moderate depression (strong scientific evidence). Due to either side effects or lack of effectiveness, initial antidepressant treatment produces unsatisfactory results in an average of one third of the patients (strong scientific evidence). Once antidepressant treatment has resulted in remission, there is a high risk of relapse unless the same dosage is prescribed for at least another 6 months (strong scientific evidence). Extension of the treatment to 1 year further reduces the risk of relapse. Prophylactic antidepressant treatment for as long as 3 years reduces the risk of recurrence by 50 percent in patients who suffer frequent or particularly severe depressive episodes (strong scientific evidence). Sudden discontinuation of treatment with SSRIs, or TCAs that affect serotonin uptake, can cause severe withdrawal symptoms (moderately strong scientific evidence). But these symptoms do not indicate dependence, given that its classic signs – such as a significant dosage increase, preoccupation with tablet intake, or neglect of work, friends and normal interests – are absent. Antidepressants are more effective than psychotherapy for the treatment of chronic low-grade depression (dysthymia) (strong scientific evidence). ECT is safe and effective, both more rapid and more effective than antidepressant treatment (strong scientific evidence). But there is a high probability of relapse, and only limited knowledge is available about which antidepressants are effective in preventing relapse (moderately strong scientific evidence). Transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS) are experimental treatments that lack sufficient scientific basis for use in routine medical care. Light therapy has not been shown to be significantly more effective than placebos for treating seasonal affective disorder. St. John's Wort (Hypericum perforatum) has been shown to be effective for short-term and mild depression (moderately strong scientific evidence), but its effectiveness in long-term treatment has not been studied. The preparation increases the metabolism of many common medications (including cholesterol lowering drugs, anticoagulants, oral contraceptives and immunosupressive drugs following organ transplants), as a result of which their effectiveness may be reduced or eliminated. Primary care studies in several countries produced better results than routine medical care when the provider offered patient instruction, telephone support and computerized reminders about treatment protocols, as well as ready access to psychiatrists and psychologists trained in short-term psychotherapy (strong scientific evidence). One antidepressant, (fluoxetine), has been shown to be effective for short-term treatment of depression in children and adolescents (moderately strong scientific evidence). No antidepressant has been approved in Sweden for treating that age group. Controlled long-term trials are completely lacking, though the risk of relapse after short-term treatment is just as high as in adults. There is moderate scientific support for treating depression in children and adolescents with cognitive behavioral therapy and interpersonal psychotherapy (moderately strong scientific evidence), but the long-term effectiveness is insufficiently documented. The effectiveness of antidepressant treatment and psychotherapy in the elderly up to the age of 75 is well documented (strong scientific evidence), but there are no studies of people over 80. Research on effective treatments for bipolar disorder has been very limited, and the results of the numerous trials now under way are not expected for several years. Lithium has been proven to be the most effective drug for the acute treatment of both manic and depressive episodes, as well as for preventive treatment (strong scientific evidence). Several new antipsychotic drugs have also been proven to be effective with acute manic episodes (strong scientific evidence), but there is only moderately strong scientific evidence for their preventive effect (moderately strong scientific evidence). Although some drugs originally developed to treat epilepsy are effective with both mania and depression (strong scientific evidence), only lamotrigine has been shown to have a preventive effect, primarily against depressive episodes (strong scientific evidence). There are several key areas in which research provides no basis for choosing a particular treatment. Studies are totally lacking when it comes to treating depression in people over 80. There are no studies of antidepressant treatment in children and adolescents that have lasted longer than 10 weeks, and documentation of the long-term effectiveness of psychotherapy in these age groups is very limited.

2004 03

https://www.ncbi.nlm.nih.gov/pubmed/?term=28876724

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Transcranial low-level laser therapy improves brain mitochondrial function and cognitive impairment in D-galactose-induced aging mice.

Salehpour F, Ahmadian N, Rasta SH, Farhoudi M, Karimi P, Sadigh-Eteghad S

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz, Iran; School of Medical Sciences, University of Aberdeen, Aberdeen, UK. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: Saeed.sadigetegad@gmail.com..

Mitochondrial function plays a key role in the aging-related cognitive impairment, and photoneuromodulation of mitochondria by transcranial low-level laser therapy (LLLT) may contribute to its improvement. This study focused on the transcranial LLLT effects on the D-galactose (DG)-induced mitochondrial dysfunction, apoptosis, and cognitive impairment in mice. For this purpose, red and near-infrared (NIR) laser wavelengths (660 and 810 nm) at 2 different fluencies (4 and 8 J/cm(2)) at 10-Hz pulsed wave mode were administrated transcranially 3 d/wk in DG-received (500 mg/kg/subcutaneous) mice model of aging for 6 weeks. Spatial and episodic-like memories were assessed by the Barnes maze and What-Where-Which (WWWhich) tasks. Brain tissues were analyzed for mitochondrial function including active mitochondria, adenosine triphosphate, and reactive oxygen species levels, as well as membrane potential and cytochrome c oxidase activity. Apoptosis-related biomarkers, namely, Bax, Bcl-2, and caspase-3 were evaluated by Western blotting method. Laser treatments at wavelengths of 660 and 810 nm at 8 J/cm(2) attenuated DG-impaired spatial and episodic-like memories. Also, results showed an obvious improvement in the mitochondrial function aspects and modulatory effects on apoptotic markers in aged mice. However, same wavelengths at the fluency of 4 J/cm(2) had poor effect on the behavioral and molecular indexes in aging model. This data indicates that transcranial LLLT at both of red and NIR wavelengths at the fluency of 8 J/cm(2) has a potential to ameliorate aging-induced mitochondrial dysfunction, apoptosis, and cognitive impairment.

Neurobiol Aging 2017 58 140-150

https://www.ncbi.nlm.nih.gov/pubmed/?term=28735143

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Photoactivation of ERK/CREB/VMAT2 pathway attenuates MPP(+)-induced neuronal injury in a cellular model of Parkinson’s disease.

Gu X, Liu L, Shen Q, Xing D

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address: liulei@scnu.edu.cn. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address: xingda@scnu.edu.cn..

The vesicular monoamine transporter 2 (VMAT2) pumps dopamine from cytoplasm into synaptic vesicles for subsequent release, and the deficits of VMAT2 has been implicated in the dopaminergic neuronal cell loss which is considered as a typical pathological feature of Parkinson’s disease (PD). Low-power laser irradiation (LPLI), a potent noninvasive physiotherapy approach, is capable of penetrating into nerve tissue to exert beneficial effects such as promoting nerve regeneration and ATP production. In the present study, we demonstrated that LPLI protects against MPP(+)-induced neurotoxicity via upregulation of VMAT2 in SH-SY5Y human dopaminergic neuroblastoma cells. The photoactivation of ERK phosphorylated cAMP-response element binding protein (CREB) at Ser133, and thus increased the ability of CREB binding to the promoter region of VMAT2, leading to elevated VMAT2 expression, which contributes to dopamine release and cell survival. Taken together, for the first time to our knowledge, the results showed that LPLI attenuates MPP(+)-induced neurotoxicity through activation of ERK/CREB/VMAT2 pathway, suggesting that the manipulation of VMAT2 by LPLI may provide a potential therapeutic strategy for PD.

Cell Signal 2017 Jun 13 37 103-114

https://www.ncbi.nlm.nih.gov/pubmed/?term=28627368

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Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition.

Berman MH, Halper JP, Nichols TW, Jarrett H, Lundy A, Huang JH

P.I. Quietmind Foundation, 1016 Greenwood Ave, Wyncote PA 19095, USA. Board, Quietmind Foundation, CNDD Hanover PA 17331, USA. Board, Quietmind Foundation, CNDD Hanover PA 17331, USA. Board, Quietmind Foundation, CNDD Hanover PA 17331, USA. Department of Neurosurgery, Baylor Scott and White, Temple, Texas 76502, USA..

Alzheimer’s disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer’s disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (A ) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer’s drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600-1000 nm) was associated with a reduction in the size and number of amyloid- plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060-1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation’s institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement.

J Neurol Neurosci 2017 8(1)

https://www.ncbi.nlm.nih.gov/pubmed/?term=28593105

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Photobiomodulation and the brain: a new paradigm.

Hennessy M, Hamblin MR

Briarcliff High School, Briarcliff Manor, NY, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA. Department of Dermatology, Harvard Medical School, Boston, MA, USA. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA..

Transcranial photobiomodulation (PBM) also known as low level laser therapy (tLLLT) relies on the use of red/NIR light to stimulate, preserve and regenerate cells and tissues. The mechanism of action involves photon absorption in the mitochondria (cytochrome c oxidase), and ion channels in cells leading to activation of signaling pathways, up-regulation of transcription factors, and increased expression of protective genes. We have studied PBM for treating traumatic brain injury (TBI) in mice using a NIR laser spot delivered to the head. Mice had improved memory and learning, increased neuroprogenitor cells in the dentate gyrus and subventricular zone, increased BDNF and more synaptogenesis in the cortex. These highly beneficial effects on the brain suggest that the applications of tLLLT are much broader than at first conceived. Other groups have studied stroke (animal models and clinical trials), Alzheimer’s disease, Parkinson’s disease, depression, and cognitive enhancement in healthy subjects.

J Opt 2017 Jan 19(1) 013003

https://www.ncbi.nlm.nih.gov/pubmed/?term=28580093

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Low-level laser therapy (780 nm) combined with collagen sponge scaffold promotes repair of rat cranial critical-size defects and increases TGF- , FGF-2, OPG/RANK and osteocalcin expression.

de Oliveira LSS, de Araújo AA, de Araújo Júnior RF, Barboza CAG, Borges BCD, da Silva JSP

Department of Dentistry, Post-Graduation Program in Public Health, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Department of Biophysics and Pharmacology, Post Graduation Program in Public Health/Post Graduation Program in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Department of Morphology, Post Graduation Program in Health Science/Post Graduation Program in Functional and Structural Biology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Department of Morphology, Post-Graduation Program in Oral Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Department of Dentistry, Post-Graduation Program in Public Health, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Department of Dentistry, Post-Graduation Program in Public Health, Federal University of Rio Grande do Norte, Natal, RN, Brazil..

The aim of this study was to evaluate the effect of collagen sponge scaffold (CSS) implantation associated with low-level laser therapy (LLLT) on repairing bone defects. A single 5-mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (n = 10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (CSS) alone (G1); defect treated with low-level laser therapy (LLLT) (wavelength 780 nm; total energy density 120 J/cm(2) ; power 50 mW) alone (G2); and CSS associated with LLLT treatment (G3). After surgery, animals in each group were euthanized at 21 days and 30 days (n = 5 per euthanasia time group). Bone formation was monitored by X-ray imaging analysis. Biopsies were collected and processed for histological analysis and immunohistochemical evaluation of transforming growth factor-beta (TGF- ), fibroblast growth factor-2 (FGF-2), osteoprotegerin (OPG) and receptor activator of nuclear factor (RANK). Osteocalcin (OCN) was detected by immunofluorescence analysis. Compared to the G0 group, defects in the 30-day G3 group exhibited increased bone formation, both by increase in radiopaque areas (P < 0.01) and by histomorphometric analysis (P < 0.001). The histopathological analysis showed a decreased number of inflammatory cells (P < 0.001). The combined CCS + LLLT (G3) treatment also resulted in the most intense immunostaining for OPG, RANK, FGF-2 and TGF- , and the most intense and diffuse OCN immunofluorescent labelling at 30 days postsurgery (G3 vs. G0 group, P < 0.05). Therefore, the use of CCS associated with LLLT could offer a synergistic advantage in improving the healing of bone fractures.

Int J Exp Pathol 2017 May 29

https://www.ncbi.nlm.nih.gov/pubmed/?term=28556971

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Nonpharmacological Treatments for Post-Stroke Depression: An Integrative Review of the Literature.

Hadidi NN, Huna Wagner RL, Lindquist R

Stroke is the fifth leading cause of death and the number one cause of long-term disability. Seventy-five percent of annual stroke victims are older than 65. Post-stroke depression (PSD) is a common consequence of stroke, with the estimated prevalence ranging from 25% to 79%. Although several studies have investigated the impact of pharmacological interventions on PSD, there is a significant gap in knowledge regarding the efficacy of nonpharmacological measures for treatment of PSD. The purpose of the current integrative literature review was to synthesize the state of knowledge on selected nonpharmacological treatments for PSD and present findings regarding the efficacy of investigated treatments. Twenty-one studies published from 1992-2016 were identified and synthesized. Results indicated that studies demonstrating improvement in depressive symptoms included ecosystem-focused therapy, life review therapy, problem solving therapy, meridian acupressure, repetitive transcranial magnetic stimulation, music therapy, exercise, light therapy, motivational interviewing, and robotic-assisted neurorehabilitation. [Res Gerontol Nurs. 2017; x(x):xx-xx.].

Res Gerontol Nurs 2017 May 30 1-14

https://www.ncbi.nlm.nih.gov/pubmed/?term=28556875

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Efficacy of photobiomodulation therapy on masseter thickness and oral health-related quality of life in children with spastic cerebral palsy.

Santos MTBR, Nascimento KS, Carazzato S, Barros AO, Mendes FM, Diniz MB

Graduate Program in Dentistry, Cruzeiro do Sul University , Rua Galvão Bueno 868, Liberdade, São Paulo, SP CEP 01506-000, Brazil. drsantosmt@yahoo.com.br. Patients with Special Needs, Cruzeiro do Sul University, Rua Galvão Bueno 868, Liberdade, São Paulo-SP, 01506-000, Brazil. drsantosmt@yahoo.com.br. Associação de Assistência à Criança Deficiente (AACD), Av. Professor Ascendino Reis, 724 – Ibirapuera, São Paulo-SP, P 04027-000, Brazil. drsantosmt@yahoo.com.br. Associação de Assistência à Criança Deficiente (AACD), Av. Professor Ascendino Reis, 724 – Ibirapuera, São Paulo-SP, P 04027-000, Brazil. Associação de Assistência à Criança Deficiente (AACD), Av. Professor Ascendino Reis, 724 – Ibirapuera, São Paulo-SP, P 04027-000, Brazil. Graduate Program in Dentistry, Cruzeiro do Sul University , Rua Galvão Bueno 868, Liberdade, São Paulo, SP CEP 01506-000, Brazil. Sergipe Federal University, Hospital Universitario (HU), Campus Prof. João Cardoso Nascimento Rua Cláudio Batista, s/n, Cidade Nova, Aracaju, SE CEP 49060-108, Brazil. School of Dentistry, São Paulo University (USP), Av. Prof. Lineu Prestes 2227 Cidade Universitária, São Paulo, SP CEP 05508-900, Brazil. Graduate Program in Dentistry, Cruzeiro do Sul University , Rua Galvão Bueno 868, Liberdade, São Paulo, SP CEP 01506-000, Brazil..

The study aimed to evaluate the efficacy of photobiomodulation therapy (PBMT) on bilateral masseter muscle thickness and amplitude of mouth opening in children with spastic cerebral palsy (CP), and the impact on their oral health-related quality of life (OHRQOL). Three groups were included: experimental CP group (EG: n = 26 with oral complaints), positive control CP group (PCG: n = 26 without complaints), and negative control group (NCG: n = 26 without CP). In the EG, the masseter muscles on both sides were irradiated with an infrared low-level Ga-Al-As laser ( = 808 ± 3 nm, 120 mW) using a 3 J/cm(2) energy dose per site, with a 20 s exposure time per site (spot area: 4 mm(2); irradiance: 3 W/cm(2); energy delivery per point: 2.4 J) six times over six consecutive weeks. Masseter thickness, assessed through ultrasonography, and the amplitude of mouth opening were measured in the EG before and after six applications of PBMT and once in the PCG and NCG. The Parental-Caregiver Perception Questionnaire (P-CPQ) was used to evaluate OHRQOL. ANOVA, chi-square, t tests, and multilevel linear regression were used for statistical analysis. In the EG, the study results revealed average increments of 0.77 (0.08) millimeter in masseter thickness (P < 0.05) and 7.39 (0.58) millimeter for mouth opening (P < 0.05) and reduction in all P-CPQ domains (P < 0.001), except for social well-being. The six applications of PBMT increased masseter thickness and mouth opening amplitude and reduced the impact of spastic CP on OHRQOL.

Lasers Med Sci 2017 May 23

https://www.ncbi.nlm.nih.gov/pubmed/?term=28536904

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Comparison of low level laser therapy and interferential current on post stroke shoulder pain.

Jan F, Naeem A, Malik AN, Amjad I, Malik T

Armed Forces Institute of Rehabilitation, Rawalpindi, Pakistan. Riphah College of Rehabilitation Sciences, Riphah International University, Islamabad, Pakistan. Riphah College of Rehabilitation Sciences, Riphah International University, Islamabad, Pakistan. Riphah College of Rehabilitation Sciences, Riphah International University, Islamabad, Pakistan. Armed Forces Institute of Rehabilitation, Rawalpindi, Pakistan..

The objective of the study was to compare the effects of LASER therapy and Interferential current on post stroke shoulder pain. Diagnosed patients (n=38) of post stroke shoulder pain were randomly divided into two groups i.e., LASER group (LG =20 patients) and Interferential current group (IFCG=18 patients). The variables under study were pain, satisfaction, disability, and function level before and after treatment. Improvement in pain and satisfaction level after LASER therapy was significant (p<0.001). However improvement in functional level was not significant (p> 0.05). The study findings revealed that LASER therapy is more effective than Interferential current in decreasing pain and increasing satisfaction level of stroke patients having shoulder pain.

J Pak Med Assoc 2017 May 67(5) 788-789

https://www.ncbi.nlm.nih.gov/pubmed/?term=28507373

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Photostimulation of mitochondria as a treatment for retinal neurodegeneration.

Beirne K, Rozanowska M, Votruba M

School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK; Cardiff Institute for Tissue Engineering and Repair, Cardiff University, Cardiff, UK. Electronic address: BeirneK@cardiff.ac.uk. School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK; Cardiff Institute for Tissue Engineering and Repair, Cardiff University, Cardiff, UK. Electronic address: RozanowskaMB@cardiff.ac.uk. School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK; Cardiff Institute for Tissue Engineering and Repair, Cardiff University, Cardiff, UK; Cardiff Eye Unit, University Hospital of Wales, Cardiff, UK. Electronic address: VotrubaM@cardiff.ac.uk..

Absorption of photon energy by neuronal mitochondria leads to numerous downstream neuroprotective effects. Red and near infrared (NIR) light are associated with significantly less safety concerns than light of shorter wavelengths and they are therefore, the optimal choice for irradiating the retina. Potent neuroprotective effects have been demonstrated in various models of retinal damage, by red/NIR light, with limited data from human studies showing its ability to improve visual function. Improved neuronal mitochondrial function, increased blood flow to neural tissue, upregulation of cell survival mediators and restoration of normal microglial function have all been proposed as potential underlying mechanisms of red/NIR light.

Mitochondrion 2017 May 09

https://www.ncbi.nlm.nih.gov/pubmed/?term=28499983

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Beneficial neurocognitive effects of transcranial laser in older adults.

Vargas E, Barrett DW, Saucedo CL, Huang LD, Abraham JA, Tanaka H, Haley AP, Gonzalez-Lima F

Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA. Department of Electrical Engineering, University of Texas at Austin, Austin, TX, 78712, USA. Department of Electrical Engineering, University of Texas at Austin, Austin, TX, 78712, USA. Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, 78712, USA. Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA. Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA. gonzalezlima@utexas.edu..

Transcranial infrared laser stimulation (TILS) at 1064 nm, 250 mW/cm(2) has been proven safe and effective for increasing neurocognitive functions in young adults in controlled studies using photobiomodulation of the right prefrontal cortex. The objective of this pilot study was to determine whether there is any effect from TILS on neurocognitive function in older adults with subjective memory complaint at risk for cognitive decline (e.g., increased carotid artery intima-media thickness or mild traumatic brain injury). We investigated the cognitive effects of TILS in older adults (ages 49-90, n = 12) using prefrontal cortex measures of attention (psychomotor vigilance task (PVT)) and memory (delayed match to sample (DMS)), carotid artery intima-media thickness (measured by ultrasound), and evaluated the potential neural mechanisms mediating the cognitive effects of TILS using exploratory brain studies of electroencephalography (EEG, n = 6) and functional magnetic resonance imaging (fMRI, n = 6). Cognitive performance, age, and carotid artery intima-media thickness were highly correlated, but all participants improved in all cognitive measures after TILS treatments. Baseline vs. chronic (five weekly sessions, 8 min each) comparisons of mean cognitive scores all showed improvements, significant for PVT reaction time (p < 0.001), PVT lapses (p < 0.001), and DMS correct responses (p < 0.05). The neural studies also showed for the first time that TILS increases resting-state EEG alpha, beta, and gamma power and promotes more efficient prefrontal blood-oxygen-level-dependent (BOLD)-fMRI response. Importantly, no adverse effects were found. These preliminary findings support the use of TILS for larger randomized clinical trials with this non-invasive approach to augment neurocognitive function in older people to combat aging-related and vascular disease-related cognitive decline.

Lasers Med Sci 2017 May 02

https://www.ncbi.nlm.nih.gov/pubmed/?term=28466195

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Low-level light emitting diode therapy promotes long-term functional recovery after experimental stroke in mice.

Lee HI, Lee SW, Kim NG, Park KJ, Choi BT, Shin YI, Shin HK

Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam, 50612, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Medical Research Center of Color Seven, Seoul, 06719, Republic of Korea. Medical Research Center of Color Seven, Seoul, 06719, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam, 50612, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, 50612, Republic of Korea..

We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU(+) ) in the ischemic brain, and significant increases in BrdU(+) /GFAP(+) , BrdU(+) /DCX(+) , BrdU(+) /NeuN(+) , and CD31(+) cells in the subacute LED-T group. However, the BrdU(+) /Iba-1(+) cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia.

J Biophotonics 2017 May 02

https://www.ncbi.nlm.nih.gov/pubmed/?term=28464523

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Laser Acupuncture Exerts Neuroprotective Effects via Regulation of Creb, Bdnf, Bcl-2, and Bax Gene Expressions in the Hippocampus.

Yun YC, Jang D, Yoon SB, Kim D, Choi DH, Kwon OS, Lee YM, Youn D

Department of Meridian and Acupuncture Point, College of Korean Medicine, Dongshin University, 185, Geonjae-ro, Naju, Republic of Korea. Acupuncture, Moxibustion, and Acupuncture Point Research Group, Korea Institute of Oriental Medicine, 1672, Yuseong-daero, Yuseong-gu, Daejeon, Republic of Korea. Department of Meridian and Acupuncture Point, College of Korean Medicine, Dongshin University, 185, Geonjae-ro, Naju, Republic of Korea. Department of Meridian and Acupuncture Point, College of Korean Medicine, Dongshin University, 185, Geonjae-ro, Naju, Republic of Korea..

Acupuncture has a positive effect on cognitive deficits. However, the effects of laser acupuncture (LA) on cognitive function and its mechanisms of action are unclear. The present study aimed to evaluate the effects of LA on middle cerebral artery occlusion- (MCAO-) induced cognitive impairment and its mechanisms of action. Transient focal cerebral ischemia was modeled in adult Sprague-Dawley rats by MCAO. After LA or manual-acupuncture (MA) treatment at the GV20 and HT7 for 2 weeks, hippocampal-dependent memory was evaluated using the Morris water maze (MWM) test. The hippocampus was dissected to analyze choline acetyltransferase (ChAT) immunoreactivity and Creb, Bdnf, Bcl-2, and Bax gene expressions. MWM test demonstrated a significant improvement in hippocampal-dependent memory in the MCAO rats after LA treatment. LA treatment significantly reversed the postischemic decrease in ChAT immunoreactivity in the hippocampal CA1 region. LA treatment significantly normalized gene expression in the hippocampus which had been altered by MCAO, especially upregulating gene expression of Creb, Bdnf, and Bcl-2 and downregulating gene expression of Bax. This study suggests that LA treatment could improve cognitive impairment in MCAO rats to enhance the cholinergic system in the hippocampal CA1 region and to exert a neuroprotective effect by regulating Creb, Bdnf, Bcl-2, and Bax gene expressions.

Evid Based Complement Alternat Med 2017 2017 7181637

https://www.ncbi.nlm.nih.gov/pubmed/?term=28408940

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Evaluation of the bony repair in rat cranial defect using near infrared reflectance spectroscopy and discriminant analysis.

de Lima LAS, Lima KMG, de Oliveira LSS, Araújo AA, Fernandes de Araújo Junior R

Div. of Analytical Chemistry, Inst. of Chemistry, Biological Chemistry and Chemometrics, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil. Dept. of Biophysics and Pharmacology, Post-graduation programme in Public Health/Post graduation programme in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil. Dept. of Biophysics and Pharmacology, Post-graduation programme in Public Health/Post graduation programme in Pharmaceutical Science, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil. Dept. of Morphology, Post-graduation programme in Health Science/Post graduation programme in Structural and Functional Biology, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil..

We set out to determine whether near infrared reflectance spectroscopy (NIRS) combined with principal component analysis-linear discriminant analysis (LDA) or, variable selection techniques employing successive projection algorithm or genetic algorithm (GA) could evaluate the bone repair in cranial critical-size (5 mm) defect after stimulation with collagen sponge scaffold and/or infrared low-level laser therapy directly on the local. Forty-five Winstar rats were divided into nine groups of five each, namely: group H – healthy, n = 5 (without treatment and without cranial critical-size defect), (GI positive control – n = 5, 21 days or n = 5, 30 days) without treatment and with cranial critical-size defect; (GII-n = 5, 21 days or n = 5, 30 days) cranial critical-size defect filled with collagen sponge scaffold; (GIII-n = 5, 21 days or n = 5, 30 days) cranial critical-size defect submitted to low-level laser therapy; (GIV-n = 5, 21 days or n = 5, 30 days) cranial critical-size defect submitted to combined collagen sponge scaffold + low-level laser therapy treatment. In relation to the histological analysis, the collagen sponge scaffold + low-level laser therapy treatment group (GIV) 30 days showed the best result with the presence of secondary bone, immature bone (osteoid) and newly formed connective tissue (periosteum). GA-LDA model also successfully classified control class of the others classes. Thus, the results provided by the good-quality classification model revealed the feasibility of NIRS for application to evaluation of the wound healing in rat cranial defect, thanks to the short analysis time of a few seconds and nondestructive advantages of NIRS as an alternative approach for bone repair purposes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 2017.

Biotechnol Prog 2017 Apr 03

https://www.ncbi.nlm.nih.gov/pubmed/?term=28371519

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Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms.

Lee HI, Lee SW, Kim SY, Kim NG, Park KJ, Choi BT, Shin YI, Shin HK

Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea. Medical Research Center of Color Seven, Seoul 06719, Republic of Korea. Medical Research Center of Color Seven, Seoul 06719, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea. Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: rmshin01@gmail.com. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: julie@pusan.ac.kr..

Photostimulation with low-level light emitting diode therapy (LED-T) modulates neurological and psychological functions. The purpose of this study was to evaluate the effects of LED-T pretreatment on the mouse brain after ischemia/reperfusion and to investigate the underlying mechanisms. Ischemia/reperfusion brain injury was induced by middle cerebral artery occlusion. The mice received LED-T twice a day for 2 days prior to cerebral ischemia. After reperfusion, the LED-T group showed significantly smaller infarct and edema volumes, fewer behavioral deficits compared to injured mice that did not receive LED-T and significantly higher cerebral blood flow compared to the vehicle group. We observed lower levels of endothelial nitric oxide synthase (eNOS) phosphorylation in the injured mouse brains, but significantly higher eNOS phosphorylation in LED-T-pretreated mice. The enhanced phospho-eNOS was inhibited by LY294002, indicating that the effects of LED-T on the ischemic brain could be attributed to the upregulation of eNOS phosphorylation through the phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, no reductions in infarct or edema volume were observed in LED-T-pretreated eNOS-deficient (eNOS(-/-)) mice. Collectively, we found that pretreatment with LED-T reduced the amount of ischemia-induced brain damage. Importantly, we revealed that these effects were mediated by the stimulation of eNOS phosphorylation via the PI3K/Akt pathway.

Biochem Biophys Res Commun 2017 May 13 486(4) 945-950

https://www.ncbi.nlm.nih.gov/pubmed/?term=28347821

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Primary Localized Cutaneous Amyloidosis: A Systematic Treatment Review.

Weidner T, Illing T, Elsner P

Department of Dermatology, University Hospital Jena, Erfurter Straße 35, Jena, 07743, Germany. till.weidner@med.uni-jena.de. Department of Dermatology, University Hospital Jena, Erfurter Straße 35, Jena, 07743, Germany. Department of Dermatology, University Hospital Jena, Erfurter Straße 35, Jena, 07743, Germany..

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA. OBJECTIVE: The aim of this study was to review the current reported treatment options for PLCA. METHODS: This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016. RESULTS: Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D3 analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy. CONCLUSION: No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.

Am J Clin Dermatol 2017 Mar 24

https://www.ncbi.nlm.nih.gov/pubmed/?term=28342017

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Light-Emitting Diode (LED) therapy improves occipital cortex damage by decreasing apoptosis and increasing BDNF-expressing cells in methanol-induced toxicity in rats.

Ghanbari A, Ghareghani M, Zibara K, Delaviz H, Ebadi E, Jahantab MH

Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran. ER045, Laboratory of Stem Cells, DSST, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon. Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran. Electronic address: delavizhamdi83@gmail.com. Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran. Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran..

Methanol-induced retinal toxicity, frequently associated with elevated free radicals and cell edema, is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Previous studies investigated the effect of photomodulation on RGCs, but not the visual cortex. In this study, the effect of 670nm Light-Emitting Diode (LED) therapy on RGCs and visual cortex recovery was investigated in a seven-day methanol-induced retinal toxicity protocol in rats. Methanol administration showed a reduction in the number of RGCs, loss of neurons (neuronal nuclear antigen, NeuN+), activation of glial fibrillary acidic protein (GFAP+) expressing cells, suppression of brain-derived neurotrophic factor (BDNF+) positive cells, increase in apoptosis (caspase 3+) and enhancement of nitric oxide (NO) release in serum and brain. On the other hand, LED therapy significantly reduced RGC death, in comparison to the methanol group. In addition, the number of BDNF positive cells was significantly higher in the visual cortex of LED-treated group, in comparison to methanol-intoxicated and control groups. Moreover, LED therapy caused a significant decrease in cell death (caspase 3+ cells) and a significant reduction in the NO levels, both in serum and brain tissue, in comparison to methanol-intoxicated rats. Overall, LED therapy demonstrated a number of beneficial effects in decreasing oxidative stress and in functional recovery of RGCs and visual cortex. Our data suggest that LED therapy could be a potential condidate as a non-invasive approach for treatment of retinal damage, which needs further clinicl studies.

Biomed Pharmacother 2017 May 89 1320-1330

https://www.ncbi.nlm.nih.gov/pubmed/?term=28320099

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Photobiomodulation-induced changes in a monkey model of Parkinson’s disease: changes in tyrosine hydroxylase cells and GDNF expression in the striatum.

El Massri N, Lemgruber AP, Rowe IJ, Moro C, Torres N, Reinhart F, Chabrol C, Benabid AL, Mitrofanis J

Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. john.mitrofanis@sydney.edu.au..

Intracranial application of red to infrared light, known also as photobiomodulation (PBM), has been shown to improve locomotor activity and to neuroprotect midbrain dopaminergic cells in rodent and monkey models of Parkinson’s disease. In this study, we explored whether PBM has any influence on the number of tyrosine hydroxylase (TH)(+)cells and the expression of GDNF (glial-derived neurotrophic factor) in the striatum. Striatal sections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice and monkeys and 6-hydroxydopamine (6OHDA)-lesioned rats that had PBM optical fibres implanted intracranially (or not) were processed for immunohistochemistry (all species) or western blot analysis (monkeys). In our MPTP monkey model, which showed a clear loss in striatal dopaminergic terminations, PBM generated a striking increase in striatal TH(+) cell number, 60% higher compared to MPTP monkeys not treated with PBM and 80% higher than controls. This increase was not evident in our MPTP mouse and 6OHDA rat models, both of which showed minimal loss in striatal terminations. In monkeys, the increase in striatal TH(+) cell number in MPTP-PBM cases was accompanied by similar increases in GDNF expression, as determined from western blots, from MPTP and control cases. In summary, these results offer insights into the mechanisms by which PBM generates its beneficial effects, potentially with the use of trophic factors, such as GDNF.

Exp Brain Res 2017 Mar 15

https://www.ncbi.nlm.nih.gov/pubmed/?term=28299414

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Transcranial LED therapy on amyloid-_ toxin 25-35 in the hippocampal region of rats.

da Luz EltchechemC, SalgadoAS, ZângaroRA, da Silva PereiraMC, KerppersII, da SilvaLA, ParreiraRB

Laboratory of Neuroanatomy and Neurophysiology for the Physiotherapy, Universidade Estadual do Centro-Oeste, Rua Simeão Camargo Varela de Sá, 03, Guarapuava, Paraná, Brazil, 85040-080. School of Postural and Manual Therapy, Salgado Institute of Integral H.

Excessive A deposition in the brain is associated with the formation of senile plaques, and their diffuse distribution is related to Alzheimer’s disease. Thirty rats (EG) were irradiated with light-emitting diode (photobiomodulation (PBM)) in the frontal region of the skull after being inoculated with the A toxin in the hippocampus; 30 rats were used as the control group (CG). The analysis was conducted at 7, 14, and 21 days after irradiation. We observed a decreased in A deposits in treated animals compared with animals in the CG. The behavioral and motor assessment revealed that the EG group covered a larger ground distance and explored the open field than the CG group on days 14 and 21 (p < 0.05). The EG group was statistically significant in the spatial memory test compared to the CG group on day 14. The use of PBM significantly reduced the presence of A plaques and improved spatial memory and behavioral and motor skills in treated animals on day 21.

Lasers Med Sci 2017 Mar 02

https://www.ncbi.nlm.nih.gov/pubmed/?term=28255783

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The potential of transcranial photobiomodulation therapy for treatment of major depressive disorder.

Salehpour F, Rasta SH

Major depressive disorder is a common debilitating mood disorder that affects quality of life. Prefrontal cortex abnormalities, an imbalance in neurotransmitters, neuroinflammation, and mitochondrial dysfunction are the major factors in the etiology of major depressive disorder. Despite the efficacy of pharmacotherapy in the treatment of major depressive disorder, 30%-40% of patients do not respond to antidepressants. Given this, exploring the alternative therapies for treatment or prevention of major depressive disorder has aroused interest among scientists. Transcranial photobiomodulation therapy is the use of low-power lasers and light-emitting diodes in the far-red to near-infrared optical region for stimulation of neuronal activities. This non-invasive modality improves the metabolic capacity of neurons due to more oxygen consumption and ATP production. Beneficial effects of transcranial photobiomodulation therapy in the wide range of neurological and psychological disorders have been already shown. In this review, we focus on some issues relating to the application of photobiomodulation therapy for major depressive disorder. There is some evidence that transcranial photobiomodulation therapy using near-infrared light on 10-Hz pulsed mode appears to be a hopeful technique for treatment of major depressive disorder. However, further studies are necessary to find the safety of this method and to determine its effective treatment protocol.

Rev Neurosci 2017 Feb 23

https://www.ncbi.nlm.nih.gov/pubmed/?term=28231069

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Treating cognitive impairment with transcranial low level laser therapy.

de la Torre JC

Department of Psychology, University of Texas at Austin, 1 University Station, Austin, TX 78712-0187, United States. Electronic address: jcdelatorre@comcast.net..

This report examines the potential of low level laser therapy (LLLT) to alter brain cell function and neurometabolic pathways using red or near infrared (NIR) wavelengths transcranially for the prevention and treatment of cognitive impairment. Although laser therapy on human tissue has been used for a number of medical conditions since the late 1960s, it is only recently that several clinical studies have shown its value in raising neurometabolic energy levels that can improve cerebral hemodynamics and cognitive abilities in humans. The rationale for this approach, as indicated in this report, is supported by growing evidence that neurodegenerative damage and cognitive impairment during advanced aging is accelerated or triggered by a neuronal energy crisis generated by brain hypoperfusion. We have previously proposed that chronic brain hypoperfusion in the elderly can worsen in the presence of one or more vascular risk factors, including hypertension, cardiac disease, atherosclerosis and diabetes type 2. Although many unanswered questions remain, boosting neurometabolic activity through non-invasive transcranial laser biostimulation of neuronal mitochondria may be a valuable tool in preventing or delaying age-related cognitive decline that can lead to dementia, including its two major subtypes, Alzheimer’s and vascular dementia. The technology to achieve significant improvement of cognitive dysfunction using LLLT or variations of this technique is moving fast and may signal a new chapter in the treatment and prevention of neurocognitive disorders.

J Photochem Photobiol B 2017 Feb 13 168 149-155

https://www.ncbi.nlm.nih.gov/pubmed/?term=28219828

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Effects of Near-Infrared Light on Cerebral Bioenergetics Measured with Phosphorus Magnetic Resonance Spectroscopy.

Mintzopoulos D, Gillis TE, Tedford CE, Kaufman MJ

1 McLean Imaging Center , McLean Hospital, Harvard Medical School, Belmont, Massachusetts. 2 LumiThera, Inc. , Poulsbo, Washington. 1 McLean Imaging Center , McLean Hospital, Harvard Medical School, Belmont, Massachusetts..

OBJECTIVE: Cerebral photobiomodulation (PBM) improves mood and cognition. Cerebral metabolic enhancement is a mechanism proposed to underlie PBM effects. No PBM studies to date have applied phosphorus magnetic resonance spectroscopy (31P MRS), which can be used to assess metabolic intermediates such as phosphocreatine (PCr) and adenosine triphosphate, the latter of which is elevated by PBM. Accordingly, we used 9.4 Tesla 31P MRS to characterize effects of single and repeat cerebral PBM treatments on metabolism. PBM was delivered to healthy adult beagles in the form of transcranial laser treatment (TLT) at a wavelength of 808 nm, which passes safely through the skull and activates cytochrome C oxidase, a mitochondrial respiratory chain enzyme. METHODS: Isoflurane-anesthetized subjects (n = 4) underwent a baseline 31P MRS scan followed by TLT applied sequentially for 2 min each to anterior and posterior cranium midline locations, to irradiate the dorsal cortex. Subjects then underwent 31P MRS scans for 2 h to assess acute TLT effects. After 2 weeks of repeat TLT (3 times/week), subjects were scanned again with 31P MRS to characterize effects of repeat TLT. RESULTS: TLT did not induce acute 31P MRS changes over the course of 2 h in either scan session. However, after repeat TLT, the baseline PCr/ -nucleoside triphosphate ratio was higher than the scan 1 baseline (p < 0.0001), an effect attributable to increased PCr level (p < 0.0001). CONCLUSIONS: Our findings are consistent with reports that bioenergetic effects of PBM can take several hours to evolve. Thus, in vivo 31P MRS may be useful for characterizing bioenergetic effects of PBM in brain and other tissues.

Photomed Laser Surg 2017 Feb 09

https://www.ncbi.nlm.nih.gov/pubmed/?term=28186868

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Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report.

Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L

1 Saltmarche Health & Associates, Inc. , Orangeville, Ontario, Canada . 2 VA Boston Healthcare System , Boston, Massachusetts. 3 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts. 4 STAT-TU, Inc. , Toronto, Ontario, Canada . 5 Harvard Medical School , Boston, Massachusetts. 6 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston, Massachusetts. 7 Vielight, Inc. , Toronto, Ontario, Canada ..

OBJECTIVE: This study investigated whether patients with mild to moderately severe dementia or possible Alzheimer’s disease (AD) with Mini-Mental State Exam (MMSE) Baseline scores of 10-24 would improve when treated with near-infrared photobiomodulation (PBM) therapy. BACKGROUND: Animal studies have presented the potential of PBM for AD. Dysregulation of the brain’s default mode network (DMN) has been associated with AD, presenting the DMN as an identifiable target for PBM. MATERIALS AND METHODS: The study used 810 nm, 10 Hz pulsed, light-emitting diode devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN (bilateral mesial prefrontal cortex, precuneus/posterior cingulate cortex, angular gyrus, and hippocampus). Five patients with mild to moderately severe cognitive impairment were entered into 12 weeks of active treatment as well as a follow-up no-treatment, 4-week period. Patients were assessed with the MMSE and Alzheimer’s Disease Assessment Scale (ADAS-cog) tests. The protocol involved weekly, in-clinic use of a transcranial-intranasal PBM device; and daily at-home use of an intranasal-only device. RESULTS: There was significant improvement after 12 weeks of PBM (MMSE, p < 0.003; ADAS-cog, p < 0.023). Increased function, better sleep, fewer angry outbursts, less anxiety, and wandering were reported post-PBM. There were no negative side effects. Precipitous declines were observed during the follow-up no-treatment, 4-week period. This is the first completed PBM case series to report significant, cognitive improvement in mild to moderately severe dementia and possible AD cases.CONCLUSIONS: Results suggest that larger, controlled studies are warranted. PBM shows potential for home treatment of patients with dementia and AD.

Photomed Laser Surg 2017 Feb 10

https://www.ncbi.nlm.nih.gov/pubmed/?term=28186867

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Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

Lee HI, Lee SW, Kim NG, Park KJ, Choi BT, Shin YI, Shin HK

Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.Medical Research Center of Color Seven, Seoul 137-867, Republic of Korea.Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam 626-870, Republic of Korea.Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 626-770, Republic of Korea..

Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1 and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression.

J Biophotonics 2017 Feb 06

https://www.ncbi.nlm.nih.gov/pubmed/?term=28164443

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Neuroprotective effects of adjunctive treatments for acute stroke thrombolysis: a review of clinical evidence.

Zhou H, Huang S, Sunnassee G, Guo W, Chen J, Guo Y, Tan S

a Department of Neurology , Zhujiang Hospital of Southern Medical University , Guangzhou , China. b Department of Ultrasound , Zhujiang Hospital of Southern Medical University , Guangzhou , China. a Department of Neurology , Zhujiang Hospital of Southern Medical University , Guangzhou , China. a Department of Neurology , Zhujiang Hospital of Southern Medical University , Guangzhou , China. a Department of Neurology , Zhujiang Hospital of Southern Medical University , Guangzhou , China..

The narrow therapeutic time window and risk of intracranial hemorrhage largely restrict the clinical application of thrombolysis in acute ischemic stroke. Adjunctive treatments added to rt-PA may be beneficial to improve the capacity of neural cell to withstand ischemia, and to reduce the hemorrhage risk as well. This review aims to evaluate the neuroprotective effects of adjunctive treatments in combination with thrombolytic therapy for acute ischemic stroke. Relevant studies were searched in the PubMed, Web of Science, and EMBASE database. In this review, we first interpret the potential role of adjunctive treatments to thrombolytic therapy in acute ischemic stroke. Furthermore, we summarize the current clinical evidence for the combination of intravenous recombinant tissue plasminogen activator and various adjunctive therapies in acute ischemic stroke, either pharmaceutical or non-pharmaceutical therapy, and discuss the mechanisms of some promising treatments, including uric acid, fingolimod, minocycline, remote ischemic conditioning, hypothermia, transcranial laser therapy. Even though fingolimod, minocycline, hypothermia, and remote ischemic conditioning have yielded promising results, they still need to be rigorously investigated in further clinical trials. Further trials should also focus on neuroprotective approach with pleiotropic effects or combined agents with multiple protective mechanisms.

Int J Neurosci 2017 Jan 23 01/01/1931

https://www.ncbi.nlm.nih.gov/pubmed/?term=28110588

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Transcranial infrared laser stimulation improves rule-based, but not information-integration, category learning in humans.

Blanco NJ, Saucedo CL, Gonzalez-Lima F

Department of Psychology and Institute for Neuroscience, University of Texas at Austin, TX 78712, USA; Department of Psychology, The Ohio State University, Columbus, OH 43210, USA. Electronic address: nathanblanco@gmail.com. Department of Psychology and Institute for Neuroscience, University of Texas at Austin, TX 78712, USA. Electronic address: celestesaucedo@utexas.edu. Department of Psychology and Institute for Neuroscience, University of Texas at Austin, TX 78712, USA. Electronic address: gonzalezlima@utexas.edu..

This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation on category learning tasks. Transcranial infrared laser stimulation is a new non-invasive form of brain stimulation that shows promise for wide-ranging experimental and neuropsychological applications. It involves using infrared laser to enhance cerebral oxygenation and energy metabolism through upregulation of the respiratory enzyme cytochrome oxidase, the primary infrared photon acceptor in cells. Previous research found that transcranial infrared laser stimulation aimed at the prefrontal cortex can improve sustained attention, short-term memory, and executive function. In this study, we directly investigated the influence of transcranial infrared laser stimulation on two neurobiologically dissociable systems of category learning: a prefrontal cortex mediated reflective system that learns categories using explicit rules, and a striatally mediated reflexive learning system that forms gradual stimulus-response associations. Participants (n=118) received either active infrared laser to the lateral prefrontal cortex or sham (placebo) stimulation, and then learned one of two category structures-a rule-based structure optimally learned by the reflective system, or an information-integration structure optimally learned by the reflexive system. We found that prefrontal rule-based learning was substantially improved following transcranial infrared laser stimulation as compared to placebo (treatment X block interaction: F(1, 298)=5.117, p=0.024), while information-integration learning did not show significant group differences (treatment X block interaction: F(1, 288)=1.633, p=0.202). These results highlight the exciting potential of transcranial infrared laser stimulation for cognitive enhancement and provide insight into the neurobiological underpinnings of category learning.

Neurobiol Learn Mem 2016 Dec 27 139 69-75

https://www.ncbi.nlm.nih.gov/pubmed/?term=28039085

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Transcranial Low-Level Laser (Light) Therapy for Brain Injury.

Thunshelle C, Hamblin MR

1 Harvard College , Cambridge, Massachusetts. 2 Wellman Center for Photomedicine , Massachusetts General Hospital, Boston, Massachusetts. 2 Wellman Center for Photomedicine , Massachusetts General Hospital, Boston, Massachusetts. 3 Department of Dermatology, Harvard Medical School , Boston, Massachusetts. 4 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts..

BACKGROUND: Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI). METHODS: We review the fundamental mechanisms at the cellular and molecular level and the effects on the brain are discussed. There are several contributing processes that have been proposed to lead to the beneficial effects of PBM in treating TBI such as stimulation of neurogenesis, a decrease in inflammation, and neuroprotection. Both animal and clinical trials for ischemic stroke are outlined. A number of articles have shown how transcranial LLLT (tLLLT) is effective at increasing memory, learning, and the overall neurological performance in rodent models with TBI. RESULTS: Our laboratory has conducted three different studies on the effects of tLLLT on mice with TBI. The first studied pulsed against continuous laser irradiation, finding that 10Hz pulsed was the best. The second compared four different wavelengths, discovering only 660 and 810nm to have any effectiveness, whereas 732 and 980nm did not. The third looked at varying regimens of daily laser treatments (1, 3, and 14 days) and found that 14 laser applications was excessive. We also review several studies of the effects of tLLLT on neuroprogenitor cells, brain-derived neurotrophic factor and synaptogenesis, immediate early response knockout mice, and tLLLT in combination therapy with metabolic inhibitors. CONCLUSIONS: Finally, some clinical studies in TBI patients are covered.

Photomed Laser Surg 2016 Dec 34(12) 587-598

https://www.ncbi.nlm.nih.gov/pubmed/?term=28001759

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Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury.

Naeser MA, Martin PI, Ho MD, Krengel MH, Bogdanova Y, Knight JA, Yee MK, Zafonte R, Frazier J, Hamblin MR, Koo BB

1 VA Boston Healthcare System (12-A) , Boston, Massachusetts. 2 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.Behavioral Sciences Division, National Center for PTSD, VA Boston Healthcare System , Boston, Massachusetts. 1 VA Boston Healthcare System (12-A) , Boston, Massachusetts. 2 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts. 5 Department of Physical Medicine and Rehabilitation, Harvard Medical School , Boston, Massachusetts. 6 Spaulding Rehabilitation Hospital , Charlestown, Massachusetts. 7 Massachusetts General Hospital , Boston, Massachusetts. 8 Brigham and Women’s Hospital , Boston, Massachusetts. 9 TBI Research Program, Spaulding Rehabilitation Hospital , Charlestown, Massachusetts. 10 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston Massachusetts. 11 Department of Dermatology, Harvard Medical School , Boston, Massachusetts. 12 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts. 13 Boston University Center for Biomedical Imaging , Boston, Massachusetts..

OBJECTIVE: We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. Review of published studies: In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35cm diameter, 500mW, 22.2mW/cm(2)) was applied for 9min 45sec (13J/cm(2)) using 11 locations on the scalp: midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26J/cm(2) per LED location on the head or treated with intranasal only (iLED) using red (633nm) and NIR (810nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.

Photomed Laser Surg 2016 Dec 34(12) 610-626

https://www.ncbi.nlm.nih.gov/pubmed/?term=28001756

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The behavioural and neuroprotective outcomes when 670nm and 810nm near infrared light are applied together in MPTP-treated mice.

Reinhart F, Massri NE, Torres N, Chabrol C, Molet J, Johnstone DM, Stone J, Benabid AL, Mitrofanis J, Moro C

We have shown previously that when applied separately, 670nm and 810nm near infrared light (NIr) reduces behavioural deficits and offers neuroprotection in a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease. Here, we explored the beneficial outcomes when these NIr wavelengths were applied both together, either concurrently (at the same time) or sequentially (one after the other). Mice received MPTP injections (total of 50mg/kg) and had extracranial application of 670nm and/or 810nm NIr. Behavioural activity was tested with an open-field test and brains were processed for tyrosine hydroxylase immunohistochemistry and stereology. Our results showed that when 670nm and 810nm NIr were applied both together and sequentially, there was a greater overall beneficial outcome – increased locomotor activity and number of tyrosine hydroxylase immunoreactive cells in the substantia nigra pars compacta – than when they were applied either separately, or in particular, both together and concurrently. In summary, our findings have important implications for future use of NIr therapy in humans, that there are some combinations of wavelengths that provide more beneficial outcome than others.

Neurosci Res 2016 Nov 18

https://www.ncbi.nlm.nih.gov/pubmed/?term=27871905

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Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway.

Yan X, Liu J, Zhang Z, Li W, Sun S, Zhao J, Dong X, Qian J, Sun H

Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca(2+) imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca(2+)] i level, Bdnf mRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca(2+) release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca(2+)) stores. Blockade of Ca(2+) increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken together, these findings establish the Ca(2+)-ERK-CREB cascade as a potential signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca(2+)-dependent Bdnf mRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.

Lasers Med Sci 2016 Nov 19

https://www.ncbi.nlm.nih.gov/pubmed/?term=27864646

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Acute Effects of Near Infrared Light Therapy on Brain State in Healthy Subjects as Quantified by qEEG Measures.

Grover F, Weston J, Weston M

OBJECTIVE: Recent investigation suggests that near infrared (NIR) light may improve symptoms from mild traumatic brain injury. In addition, quantitative electroencephalography (qEEG) has shown measures correlating with concussion: P300, reaction time, and amplitude. The objective of this study was to determine whether NIR light treatment has an acute effect on brain state in healthy patients as measured by EEG. METHODS: A total of 31 healthy volunteers, between the ages of 14 and 65, underwent qEEG event-related response tests before and after a 20-min NIR light head treatment. The treatment device is composed of 784 NIR GaAIAs LEDs covering 360 cm(2) on the head in a cap covering occipital, left temporal, right temporal frontal, and parietal lobes. The fluence rate was 1 J/cm(2)·min for a power density of 16.67 mW/cm(2). Peak spectral wavelength at steady-state temperature (42.2°C) is 903 nm. The device delivered a total dose of 20 J/cm(2). Two to four months later, 18 subjects returned for a second round of qEEG measurements, with a 20-min rest period in place of the NIR light treatment as a control arm. RESULTS: Change in reaction time significantly differed between treated and control, with a mean of 23.8 msec improvement compared with controls (p = 0.035). Amplitude increased an average of 0.81 V in treatment versus 0.22 V in controls and did not reach significance. However, subanalysis of 14 treated subjects and 8 controls displaying initially low amplitude showed a mean increase in amplitude of 1.83 V (30%) in treated subjects versus 0 V in controls (p = 0.08). P300 measures did not show significant differences between groups. CONCLUSIONS: The data suggest that NIR light may have an acute effect on reaction time and amplitude in certain subject subsets. There were no adverse events registered across the 31 subjects in the treatment group, nor in the 18 evaluable control group subjects.

Photomed Laser Surg 2016 Nov 17

https://www.ncbi.nlm.nih.gov/pubmed/?term=27855264

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Low-level laser therapy for beta amyloid toxicity in rat hippocampus.

Lu Y, Wang R, Dong Y, Tucker D, Zhao N, Ahmed ME, Zhu L, Liu TC, Cohen RM, Zhang Q

Beta amyloid (A ) is well accepted to play a central role in the pathogenesis of Alzheimer’s disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on A -induced neurotoxicity in rat hippocampus. A 1-42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after A injection for 5 consecutive days. LLI treatment suppressed A -induced hippocampal neurodegeneration and long-term spatial and recognition memory impairments. Molecular studies revealed that LLI treatment: (1) restored mitochondrial dynamics, by altering fission and fusion protein levels thereby suppressing A -induced extensive fragmentation; (2) suppressed A -induced collapse of mitochondrial membrane potential; (3) reduced oxidized mitochondrial DNA and excessive mitophagy; (4) facilitated mitochondrial homeostasis via modulation of the Bcl-2-associated X protein/B-cell lymphoma 2 ratio and of mitochondrial antioxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed A -induced glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activity; (7) enhanced the total antioxidant capacity of hippocampal CA1 neurons, whereas reduced the oxidative damage; and (8) suppressed A -induced reactive gliosis, inflammation, and tau hyperphosphorylation. Although development of AD treatments has focused on reducing cerebral A levels, by the time the clinical diagnosis of AD or mild cognitive impairment is made, the brain is likely to have already been exposed to years of elevated A levels with dire consequences for multiple cellular pathways. By alleviating a broad spectrum of A -induced pathology that includes mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, and tau pathology, LLI could represent a new promising therapeutic strategy for AD.

Neurobiol Aging 2016 Oct 11 49 165-182

https://www.ncbi.nlm.nih.gov/pubmed/?term=27815990

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A new perspective on delivery of red-near-infrared light therapy for disorders of the brain.

Hart NS, Fitzgerald M

Red-near-infrared light has been used for a range of therapeutic purposes. However, clinical trials of near-infrared laser light for treatment of stroke were abandoned after failing interim futility analyses. Lack of efficacy has been attributed to sub-optimal treatment parameters and low penetrance of light to affected brain regions. Here, we assess penetrance of wavelengths from 450-880 nm in human post-mortem samples, and demonstrate that human skin, skull bone and brain transmits therapeutically relevant quantities of light from external sources at wavelengths above 600nm. Transmission through post-mortem skull bone was dependent upon thickness, and ranged from 5-12% at peak wavelengths of 700-850 nm. Transmission through brain tissue ranged from 1-7%, following an approximately linear relationship between absorbance and tissue thickness. Importantly, natural sunlight encompasses the wavelengths used in red-near-infrared light therapy. Calculations of the average irradiance of light delivered by sunlight demonstrate that sunlight can provide doses of light equivalent to — and in some cases greater than — those used in therapeutic trials. Natural sunlight could, therefore, be used as a source of therapeutic red-near-infrared light, but equally its contribution must be considered when assessing and controlling therapeutic dose in patients. For targets deep within the brain, it is unlikely that sufficient doses of light can be delivered trans-cranially; therapeutic light must be supplied via optical fibers or implanted light sources.

Discov Med 2016 Sep 22(120) 147-156

https://www.ncbi.nlm.nih.gov/pubmed/?term=27755969

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Shining light on the head: Photobiomodulation for brain disorders.

Hamblin MR

Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer’s and Parkinson’s), and psychiatric disorders (depression, anxiety, post traumatic stress disorder). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or “brain caps”. This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.

BBA Clin 2016 Dec 6 113-124

https://www.ncbi.nlm.nih.gov/pubmed/?term=27752476

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The brain effects of laser acupuncture at thirteen ghost acupoints in healthy individuals: A resting-state functional MRI investigation.

Lv J, Shi C, Deng Y, Lou W, Hu J, Shi L, Luo L, Wang D

Department of Radiology, Tianjin Nankai Hospital, Tianjin, China. Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, China. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Jinan University, Guangzhou, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; Lui Che Woo Institute of Innovation Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: shilin@cuhk.edu.hk. Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: tluop@jnu.edu.cn. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; Research Center for Medical Image Computing, Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China..

Acupuncture at thirteen ghost acupoints (TGA) was an effective treatment of neuropsychological disorders. However, the underlying neurological mechanisms of acupuncture at the TGA have not been revealed by modern scientific technologies. As laser acupuncture emerges with the painless and noninvasive advantages and the functional magnetic resonance imaging (fMRI) allows us to investigate the activation of the brain in vivo, we performed the preliminary study to investigate the relation to brain effects of acupuncture at TGA based on resting-state fMRI (rs-fMRI). Twenty one healthy subjects underwent rs-fMRI scan before and after acupuncturing TGA (except HI11 and CV1). The regional homogeneity (ReHo) values and the amplitude of low-frequency fluctuation (ALFF) values were evaluated within the whole brain and compared before and after laser stimulation of TGA. We found increased ReHo/ALFF value in serious brain regions, including right inferior occipital gyrus, bilateral middle occipital gyrus, left inferior temporal gyrus, and bilateral postcentral gyrus, after acupuncture. While, significantly decreased ReHo/ALFF value was found in the cerebellum, left superior medial frontal gyrus, left precuneus, right middle temporal gyrus, right middle frontal gyrus and left superior parietal lobule after laser stimulation. The changes in brain spontaneous function after laser acupuncture may suggest that acupuncturing at TGA may have the potential modulating effect of the cognitive functions. These preliminary findings of the changes of brain patterns at resting-state after TGA stimulation may lay the groundwork for further studies on its therapeutic effect in some neuropsychological disease models.

Comput Med Imaging Graph 2016 Aug 13

https://www.ncbi.nlm.nih.gov/pubmed/?term=27567596

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Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury.

Dong T, Zhi L, Bhayana B, Wu MX

Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, 50 Blossom Street, Boston, MA, 02114, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, 50 Blossom Street, Boston, MA, 02114, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, 50 Blossom Street, Boston, MA, 02114, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, 50 Blossom Street, Boston, MA, 02114, USA. mwu5@mgh.harvard.edu..

BACKGROUND: Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. METHODS: To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to a closed head mild TBI (mTBI) by a standard controlled cortical impact, along with or without treatment of sphingosine 1-phosphate (S1P) or rolipram, after which the brain tissue of the impact site was evaluated for cell morphology via histology, inflammation by qRT-PCR and T cell staining, and cell death with Caspase-3 and TUNEL staining. Circulating lymphocytes were quantified by flow cytometry, and plasma hydrocortisone was analyzed by LC-MS/MS. To investigate the mechanism whereby cortisol lowered the number of peripheral T cells, T cell egress was tracked in lymph nodes by intravital confocal microscopy after hydrocortisone administration. RESULTS: We detected a decreased number of circulating lymphocytes, in particular, T cells soon after mTBI, which was inversely correlated with a transient and robust increase of plasma cortisol. The transient lymphocytopenia might be caused by cortisol in part via a blockade of lymphocyte egress as demonstrated by the ability of cortisol to inhibit T cell egress from the secondary lymphoid tissues. Moreover, exogenous hydrocortisone severely suppressed periphery lymphocytes in uninjured mice, whereas administering an egress-promoting agent S1P normalized circulating T cells in mTBI mice and increased T cells in the injured brain. Likewise, rolipram, a cAMP phosphodiesterase inhibitor, was also able to elevate cAMP levels in T cells in the presence of hydrocortisone in vitro and abrogate the action of cortisol in mTBI mice. The investigation demonstrated that the number of circulating T cells in the early phase of TBI was positively correlated with T cell infiltration and inflammatory responses as well as cell death at the cerebral cortex and hippocampus beneath the impact site. CONCLUSIONS: Decreases in intracellular cAMP might be part of the mechanism behind cortisol-mediated blockade of T cell egress. The study argues strongly for a protective role of cortisol-induced immune suppression in the early stage of TBI.

J Neuroinflammation 2016 13(1) 197

https://www.ncbi.nlm.nih.gov/pubmed/?term=27561600

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Low-light-level therapy as a treatment for minimal hepatic encephalopathy: behavioural and brain assessment.

Arias N, Mendez M, Arias JL

Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK. na423@cam.ac.uk. INEUROPA, Instituto de Neurociencias del Principado de Asturias, Oviedo, Spain. na423@cam.ac.uk. Laboratorio de Neurociencias, Departamento de Psicologia, Universidad de Oviedo, Plaza Feijoo s/n, 33003, Oviedo, Spain. INEUROPA, Instituto de Neurociencias del Principado de Asturias, Oviedo, Spain. Laboratorio de Neurociencias, Departamento de Psicologia, Universidad de Oviedo, Plaza Feijoo s/n, 33003, Oviedo, Spain. INEUROPA, Instituto de Neurociencias del Principado de Asturias, Oviedo, Spain..

Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments involved in MHE. We studied one of its precipitating factors, portal hypertension. The purpose was to evaluate an enhancement in neuronal metabolism through low-light-level therapy (LLLT) and whether this therapy has effects on behavioural task acquisition. Rats were trained to perform a stimulus-response task using the Morris water maze. Three groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal vein ligation method was used to create an animal model of the early developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED light at a dose of 9 J/cm2 once a day for 7 days. The metabolic activity of the brains was studied with cytochrome c oxidase histochemistry. There were differences in behavioural performance, with an improvement in the PH + LLLT group. Energetic brain metabolism revealed significant differences between the groups in all the brain structures analysed, except the anterodorsal thalamus. At the same time, in different brain networks, the PH group showed a more complicated relationship among the structures, while the SHAM and PH + LLLT groups had similar patterns. In this study, we provide the first preliminary insights into the validity of LLLT as a possible intervention to improve memory under minimal hepatic encephalopathy conditions.

Lasers Med Sci 2016 Aug 3

https://www.ncbi.nlm.nih.gov/pubmed/?term=27488510

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Transcranial low-level infrared laser irradiation ameliorates depression induced by reserpine in rats.

Mohammed HS

Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt. Haitham@sci.cu.edu.eg..

Transcranial low-level infrared laser is a modality of therapy based on the principle of photons delivered in a non-invasive manner through the skull for the treatment of some neurological conditions such as psychological disorders, traumatic brain injuries, and neurodegenerative diseases among others. In the present study, effects of low-level infrared laser irradiation with different radiation powers (80, 200, and 400 mW, continuous wave) were investigated on normal animals subjected to forced swimming test (FST). Results indicated that there are changes in FST parameters in animals irradiated with laser; the lowest dose provoked a significant increase in animal activity (swimming and climbing) and a significant decrease in animal’s immobility, while the highest laser dose resulted in a complete inverse action by significantly increasing animal immobility and significantly decreasing animal activity with respect to control animals. The lowest dose (80 mW) of transcranial laser irradiation has then utilized on animals injected with a chronic dose of reserpine (0.2 mg/kg i.p. for 14 days) served as an animal model of depression. Laser irradiation has successfully ameliorated depression induced by reserpine as indicated by FST parameters and electrocorticography (ECoG) spectral analysis in irradiated animals. The findings of the present study emphasized the beneficial effects of low-level infrared laser irradiation on normal and healthy animals. Additionally, it indicated the potential antidepressant activity of the low dose of infrared laser irradiation.

Lasers Med Sci 2016 Jul 20

https://www.ncbi.nlm.nih.gov/pubmed/?term=27437987

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Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson’s disease.

Moro C, El Massri N, Darlot F, Torres N, Chabrol C, Agay D, Auboiroux V, Johnstone DM, Stone J, Mitrofanis J, Benabid AL

CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: cecile.moro@cea.fr. Dept of Anatomy F13, University of Sydney, 2006, Australia. Electronic address: nabil.elmassri@sydney.edu.au. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: fannie.darlot@cea.fr. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: napoleon.torres@cea.fr. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: cl.chabrol@cea.fr. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: diane.agay@cea.fr. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: vincent.auboiroux@cea.fr. Dept of Physiology F13, University of Sydney, 2006, Australia. Electronic address: daniel.johnstone@sydney.edu.au. Dept of Physiology F13, University of Sydney, 2006, Australia. Electronic address: jonathan.stone@sydney.edu.au. Dept of Anatomy F13, University of Sydney, 2006, Australia. Electronic address: john.mitrofanis@sydney.edu.au. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: alimlouis@sfr.fr..

We have reported previously that intracranial application of near-infrared light (NIr) – when delivered at the lower doses of 25J and 35J – reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson’s disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial.

Brain Res 2016 Oct 1 1648(Pt A) 19-26

https://www.ncbi.nlm.nih.gov/pubmed/?term=27396907

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Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice.

Xu Z, Guo X, Yang Y, Tucker D, Lu Y, Xin N, Zhang G, Yang L, Li J, Du X, Zhang Q, Xu X

Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China. Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, 215123, China. Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, 215123, China. Department of Psychiatry, Guangji Hospital, Suzhou City, Jiangsu, 215000, China. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA. Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China. Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China. Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, 215123, China. Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China. Department of Neurology, Suzhou Kowloon Hospital, Suzhou City, 215028, China. Department of Psychiatry, Guangji Hospital, Suzhou City, Jiangsu, 215000, China. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA. qgzhang@augusta.edu. Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu, 215004, China. xingshunxu@suda.edu.cn. Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu, 215123, China. xingshunxu@suda.edu.cn..

Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.

Mol Neurobiol 2016 Jul 5

https://www.ncbi.nlm.nih.gov/pubmed/?term=27379735

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Near-infrared light treatment reduces astrogliosis in MPTP-treated monkeys.

El Massri N, Moro C, Torres N, Darlot F, Agay D, Chabrol C, Johnstone DM, Stone J, Benabid AL, Mitrofanis J

Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. Department of Physiology F13, University of Sydney, Sydney, 2006, Australia. Department of Physiology F13, University of Sydney, Sydney, 2006, Australia. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France. Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. john.mitrofanis@sydney.edu.au..

We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson’s disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (containing the substantia nigra pars compacta; SNc) and striatum were processed for glial fibrillary acidic protein (to label astrocytes; GFAP) and ionised calcium-binding adaptor molecule 1 (to label microglia; IBA1) immunohistochemistry. Cell counts were undertaken using stereology, and cell body sizes were measured using ImageJ. Our results showed that NIr treatment reduced dramatically (~75 %) MPTP-induced astrogliosis in both the SNc and striatum. Among microglia, however, NIr had a more limited impact in both nuclei; although there was a reduction in overall cell size, there were no changes in the number of microglia in the MPTP-treated monkeys after NIr treatment. In summary, we showed that NIr treatment influenced the glial response, particularly that of the astrocytes, in our monkey MPTP model of Parkinson’s disease. Our findings raise the possibility of glial cells as a future therapeutic target using NIr.

Exp Brain Res 2016 Jul 5

https://www.ncbi.nlm.nih.gov/pubmed/?term=27377070

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Therapeutic effects of 10-HzPulsed wave lasers in rat depression model: A comparison between near-infrared and red wavelengths.

Salehpour F, Rasta SH, Mohaddes G, Sadigh-Eteghad S, Salarirad S

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz 51666, Iran. Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz 51666, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz 51666, Iran. Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz 51666, Iran. Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz 51666, Iran. School of Medical Sciences, University of Aberdeen, Aberdeen AB24 5DT, United Kingdom. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz 51666, Iran. Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz 51666, Iran. School of Medical Sciences, University of Aberdeen, Aberdeen AB24 5DT, United Kingdom. Department of Psychiatry, Tabriz University of Medical Sciences, Tabriz 51666, Iran..

BACKGROUND AND OBJECTIVE: The application of transcranial low-level light/laser therapy (tLLLT) in the range of red to near-infrared (NIR) spectrum for psychological disorders is a new area that is attracting growing interest in recent years. The photomodulation effects of NIR and red coherent lights on the activity of cytochrome c oxidase in neuronal cells of brain have been recently introduced. This study, therefore, sought to compare the therapeutic effects of 10-Hz pulsed wave NIR (810 nm) laser with red (630 nm) laser using the same delivered energy density and Citalopram in rat chronic mild stress (CMS) model of depression and anxiety. MATERIALS AND METHODS: CMS procedures (for 4 weeks) were used to induce stress. GaAlAs diode laser with red and NIR wavelengths on 10-Hz pulsed wave (50% duty cycle) were used to perform tLLLT treatment for three weeks. An energy density of about 1.2 J/cm-2 per each session was delivered through a light spot with a diameter of 3-mm to the prefrontal cortex for both wavelengths. Citalopram (10 mg/kg, Intraperitoneal) was administered for twenty-one consecutive days to the drug group. RESULTS: The findings of the present study showed an increase in swimming and decrease in immobility time, for both NIR laser and Citalopram groups compared to the stress group in forced swimming test. Anxiety-like behaviors showed insignificant decrease in all treatment groups in elevated plus maze test. The induction of stress significantly increased serum cortisol levels and treatments with both red laser and Citalopram decreased it. Hyperglycemia induced by CMS returned to normal levels in all treatment groups. The assessment of body weight also showed a significant increase in NIR laser group compared to the stress group by the end of the experiment. CONCLUSIONS: This study showed that non-invasive tLLLT using 10-Hz pulsed NIR laser light was as effective as Citalopram and more effective than red laser in the treatment of depressive-like behaviors and may help improve tLLLT as an alternative non-pharmacological treatments of psychological disorders such as depression. Lasers Surg. Med. (c) 2016 Wiley Periodicals, Inc.

Lasers Surg Med 2016 Jul 1

https://www.ncbi.nlm.nih.gov/pubmed/?term=27367569

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Dose-Finding Study of Phototherapy on Stroke Outcome in a Rabbit Model of Ischemic Stroke: Dose-Finding Phototherapy in an Ischemic Stroke Model.

Meyer DM, Chen Y, Zivin JA

Department of Neurosciences, UCSD School of Medicine, San Diego, CA, United states. Electronic address: dmmeyer@ucsd.edu. Department of Neurosciences, UCSD School of Medicine, San Diego, CA, United states. Department of Neurosciences, UCSD School of Medicine, San Diego, CA, United states..

GOAL: While transcranial laser therapy (TLT) has been shown to improve clinical outcome in a preclinical model of ischemic stroke, optimal timing and dosing has yet to be tested. The purpose of this study was to assess clinical stroke outcome in the Rabbit Small Clot Embolic Model (RSCEM) with dose escalating TLT. METHODS: We utilized the rabbit small clot embolic stroke model (RSCEM) using dose-escalating regimens. Behavioral analysis was conducted at 24hr post-embolization, allowing for the determination of the effective stroke dose (ES50) or clot amount (mg) that produces neurological deficits in 50% of a group of rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the ES50 compared with the control group. FINDINGS: A significant behavioral benefit was seen at triple TLT of 111mW treatment of 2minutes at 2hours post-embolization (6.47+/-1.06, n=17; p=0.03), compared with the previously used regimen (3.09+/-0.51, n=15). CONCLUSION: TLT results in significant behavioral improvement when administered 2hours post-embolization. Studies are warranted to evaluate this therapy in combination with thrombolysis.

Neurosci Lett 2016 Jun 21

https://www.ncbi.nlm.nih.gov/pubmed/?term=27345389

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Cerebral perfusion enhancing interventions: A new strategy for the prevention of Alzheimer dementia.

de la Torre JC

Cardiovascular and cerebrovascular disease are major risk factors in the development of cognitive impairment and Alzheimer’s disease (AD). These cardio-cerebral disorders promote a variety of vascular risk factors which in the presence of advancing age are prone to markedly reduce cerebral perfusion and create a neuronal energy crisis. Long-term hypoperfusion of the brain evolves mainly from cardiac structural pathology and brain vascular insufficiency. Brain hypoperfusion in the elderly is strongly associated with the development of mild cognitive impairment (MCI) and both conditions are presumed to be precursors of Alzheimer dementia. A therapeutic target to prevent or treat MCI and consequently reduce the incidence of AD aims to elevate cerebral perfusion using novel pharmacological agents. As reviewed here, the experimental pharmaca include the use of Rho kinase inhibitors, neurometabolic energy boosters, sirtuins and vascular growth factors. In addition, a compelling new technique in laser medicine called photobiomodulation is reviewed. Photobiomodulation is based on the use of low level laser therapy to stimulate mitochondrial energy production non-invasively in nerve cells. The use of novel pharmaca and photobiomodulation may become important tools in the treatment or prevention of cognitive decline that can lead to dementia. This article is protected by copyright. All rights reserved.

Brain Pathol 2016 Jun 20

https://www.ncbi.nlm.nih.gov/pubmed/?term=27324946

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Effects of low-level laser therapy (LLLT 808 nm) on lower limb spastic muscle activity in chronic stroke patients.

das Neves MF, Dos Reis MC, de Andrade EA, Lima FP, Nicolau RA, Arisawa EA, Andrade AO, Lima MO

Universidade do Vale do Paraiba – Laboratorio de Engenharia de Reabilotacao Sensorio Motora, Instituto de Pesquisa e Desenvolvimento, Av. Shishima Hifumi, 2911, Urbanova, Sao Jose dos Campos, SP, Brasil. mneves@univap.br. Universidade do Vale do Paraiba – Laboratorio de Engenharia de Reabilotacao Sensorio Motora, Instituto de Pesquisa e Desenvolvimento, Av. Shishima Hifumi, 2911, Urbanova, Sao Jose dos Campos, SP, Brasil. Universidade do Vale do Paraiba – Laboratorio de Engenharia de Reabilotacao Sensorio Motora, Instituto de Pesquisa e Desenvolvimento, Av. Shishima Hifumi, 2911, Urbanova, Sao Jose dos Campos, SP, Brasil. Universidade do Vale do Paraiba – Laboratorio de Engenharia de Reabilotacao Sensorio Motora, Instituto de Pesquisa e Desenvolvimento, Av. Shishima Hifumi, 2911, Urbanova, Sao Jose dos Campos, SP, Brasil. Universidade do Vale do Paraiba, Centro de Laserterapia e Fotobiologia, Instituto de Pesquisa e Desenvolvimento, Sao Jose dos Campos, SP, Brasil. Universidade do Vale do Paraiba, Laboratorio de Espectroscopia Vibracional Biomedica, Instituto de Pesquisa e Desenvolvimento, Sao Jose dos Campos, SP, Brasil. Universidade Federal de Uberlandia, Laboratorio de Engenharia Biomedica, Uberlandia, MG, Brasil. Universidade do Vale do Paraiba – Laboratorio de Engenharia de Reabilotacao Sensorio Motora, Instituto de Pesquisa e Desenvolvimento, Av. Shishima Hifumi, 2911, Urbanova, Sao Jose dos Campos, SP, Brasil..

A cerebrovascular accident (CVA) may affect basic motor functions, including spasticity that may be present in the upper extremity and/or the lower extremity, post-stroke. Spasticity causes pain, muscle force reduction, and decreases the time to onset of muscle fatigue. Several therapeutic resources have been employed to treat CVA to promote functional recovery. The clinical use of low-level laser therapy (LLLT) for rehabilitation of muscular disorders has provided better muscle responses. Thus, the aim of this study was to evaluate the effect of the application of LLLT in spastic muscles in patients with spasticity post-CVA. A double-blind clinical trial was conducted with 15 volunteer stroke patients who presented with post-stroke spasticity. Both males and females were treated; the average age was 51.5 +/- 11.8 years old; the participants entered the study ranging from 11 to 48 months post-stroke onset. The patients participated in three consecutive phases (control, placebo, and real LLLT), in which all tests of isometric endurance of their hemiparetic lower limb were performed. LLLT (diode laser, 100 mW 808 nm, beam spot area 0.0314 cm2, 127.39 J/cm2/point, 40 s) was applied before isometric endurance. After the real LLLT intervention, we observed significant reduction in the visual analogue scale for pain intensity (p = 0.0038), increased time to onset of muscle fatigue (p = 0.0063), and increased torque peak (p = 0.0076), but no significant change in the root mean square (RMS) value (electric signal in the motor unit during contraction, as obtained with surface electromyography). Our results suggest that the application of LLLT may contribute to increased recruitment of muscle fibers and, hence, to increase the onset time of the spastic muscle fatigue, reducing pain intensity in stroke patients with spasticity, as has been observed in healthy subjects and athletes.

Lasers Med Sci 2016 May 31

https://www.ncbi.nlm.nih.gov/pubmed/?term=27299571

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Low-Level Laser Therapy to the Bone Marrow Ameliorates Neurodegenerative Disease Progression in a Mouse Model of Alzheimer’s Disease: A Minireview.

Oron A, Oron U

1 Department of Orthopedic Surgery, Kaplan Medical Center , Rehovot, Israel . 2 Department of Zoology, George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University , Tel Aviv, Israel ..

OBJECTIVE: This communication reviews the ability of low-level laser therapy (LLLT) to stimulate mesenchymal stem cells (MSCs) in autologous bone marrow (BM) to enhance the capacity of MSCs to infiltrate the brain, clear beta-amyloid, and improve cognition. BACKGROUND: We recently reported that LLLT applied to the BM enhanced the proliferation of MSCs and their mobilization toward the ischemic heart region, suggesting a possible application of this approach in regenerative medicine and neurodegenerative diseases. It was also shown that circulating monocytes can infiltrate the brain and reduce brain amyloid load in an Alzheimer’s disease (AD) mouse model. METHODS AND RESULTS: MSCs from wild-type mice stimulated with LLLT demonstrated an increased ability to maturate toward a monocyte lineage and to increase phagocytosis of soluble Abeta in vitro. Furthermore, weekly LLLT for 2 months to the BM, starting at 4 months of age (progressive stage of the disease in these 5XFAD transgenic male mice), improved memory and spatial learning, compared to a sham-treated AD mouse model. Histology revealed a significant reduction in Abeta brain burden in the laser-treated mice compared to the nonlaser-treated ones. CONCLUSIONS: The application of LLLT to the BM is suggested as a therapeutic approach in progressive stages of AD, and its potential role in mediating MSC therapy in brain amyloidogenic disease is implied.

Photomed Laser Surg 2016 Jun 13

https://www.ncbi.nlm.nih.gov/pubmed/?term=27294393

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Red Light Treatment in an Axotomy Model of Neurodegeneration.

Beirne K, Rozanowska M, Votruba M

School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK. Cardiff Institute for Tissue Engineering and Repair, Cardiff University, Cardiff, UK. School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK. Cardiff Institute for Tissue Engineering and Repair, Cardiff University, Cardiff, UK. School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK. Cardiff Institute for Tissue Engineering and Repair, Cardiff University, Cardiff, UK. Cardiff Eye Unit, University Hospital of Wales, Cardiff, UK..

Red light has been shown to provide neuroprotective effects. Axotomizing the optic nerve initiates retinal ganglion cell (RGC) degeneration, and an early marker of this is dendritic pruning. We hypothesized that 670 nm light can delay axotomy-induced dendritic pruning in the retinal explant. To test this hypothesis, we monitored the effects of 670 nm light (radiant exposure of 31.7 J cm(-2) ), on RGC dendritic pruning in retinal explants from C57BL/6J mice, at 40 min, 8 h and 16 h post axotomy. For sham-treated retinae, area under the Sholl curve, peak of the Sholl curve and dendritic length at 8 h post axotomy showed statistically significant reductions by 42.3% (P = 0.008), 29.8% (P = 0.007) and 38.4% (P = 0.038), respectively, which were further reduced after 16 h by 40.56% (P < 0.008), 33.9% (P < 0.007), 45.43% (P < 0.006), respectively. Dendritic field area was also significantly reduced after 16 h, by 44.23% (P < 0.019). Such statistically significant reductions were not seen in light-treated RGCs at 8 or 16 h post axotomy. The results demonstrate the ability of 670 nm light to partially prevent ex vivo dendropathy in the mouse retina, suggesting that it is worth exploring as a treatment option for dendropathy-associated neurodegenerative diseases, including glaucoma and Alzheimer’s disease.

Photochem Photobiol 2016 Jul 92(4) 624-31

https://www.ncbi.nlm.nih.gov/pubmed/?term=27276065

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Is near-infrared light neuroprotective?

Bezard E

Institute of Neurodegenerative Diseases, University of Bordeaux and National Center for Scientific Research, Bordeaux, France..

Ann Neurol 2016 Aug 80(2) 310

https://www.ncbi.nlm.nih.gov/pubmed/?term=27273753

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Transcranial Laser Stimulation as Neuroenhancement for Attention Bias Modification in Adults with Elevated Depression Symptoms.

Disner SG, Beevers CG, Gonzalez-Lima F

Department of Psychology, The University of Texas at Austin, Austin, TX, USA; Institute for Mental Health Research, The University of Texas at Austin, Austin, TX, USA; Minneapolis VA Health Care System, Minneapolis, MN, USA. Department of Psychology, The University of Texas at Austin, Austin, TX, USA; Institute for Mental Health Research, The University of Texas at Austin, Austin, TX, USA. Electronic address: beevers@utexas.edu. Department of Psychology, The University of Texas at Austin, Austin, TX, USA; Institute for Neuroscience, The University of Texas at Austin, Austin, TX, USA..

BACKGROUND: Low-level light therapy (LLLT) with transcranial laser is a non-invasive form of neuroenhancement shown to regulate neuronal metabolism and cognition. Attention bias modification (ABM) is a cognitive intervention designed to improve depression by decreasing negative attentional bias, but to date its efficacy has been inconclusive. Adjunctive neuroenhancement to augment clinical effectiveness has shown promise, particularly for individuals who respond positively to the primary intervention. OBJECTIVE/HYPOTHESIS: This randomized, sham-controlled proof-of-principle study is the first to test the hypothesis that augmentative LLLT will improve the effects of ABM among adults with elevated symptoms of depression. METHODS: Fifty-one adult participants with elevated symptoms of depression received ABM before and after laser stimulation and were randomized to one of three conditions: right forehead, left forehead, or sham. Participants repeated LLLT two days later and were assessed for depression symptoms one and two weeks later. RESULTS: A significant three-way interaction between LLLT condition, ABM response, and time indicated that right LLLT led to greater symptom improvement among participants whose attention was responsive to ABM (i.e., attention was directed away from negative stimuli). Minimal change in depression was observed in the left and sham LLLT. CONCLUSIONS: The beneficial effects of ABM on depression symptoms may be enhanced when paired with adjunctive interventions such as right prefrontal LLLT; however, cognitive response to ABM likely moderates the impact of neuroenhancement. The results suggest that larger clinical trials examining the efficacy of using photoneuromodulation to augment cognitive training are warranted.

Brain Stimul 2016 May 24

https://www.ncbi.nlm.nih.gov/pubmed/?term=27267860

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Cognitive enhancement by transcranial laser stimulation and acute aerobic exercise.

Hwang J, Castelli DM, Gonzalez-Lima F

Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, 78712, USA. Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, 78712, USA. Department of Psychology and Institute for Neuroscience, University of Texas at Austin, 108 E. Dean Keeton Stop A8000, Austin, TX, 78712, USA. gonzalezlima@utexas.edu..

This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation and acute aerobic exercise on the same cognitive tasks. We examined whether transcranial infrared laser stimulation of the prefrontal cortex, acute high-intensity aerobic exercise, or the combination may enhance performance in sustained attention and working memory tasks. Sixty healthy young adults were randomly assigned to one of the following four treatments: (1) low-level laser therapy (LLLT) with infrared laser to two forehead sites while seated (total 8 min, 1064 nm continuous wave, 250 mW/cm2, 60 J/cm2 per site of 13.6 cm2); (2) acute exercise (EX) of high-intensity (total 20 min, with 10-min treadmill running at 85-90 % VO2max); (3) combined treatment (LLLT + EX); or (4) sham control (CON). Participants were tested for prefrontal measures of sustained attention with the psychomotor vigilance task (PVT) and working memory with the delayed match-to-sample task (DMS) before and after the treatments. As compared to CON, both LLLT and EX reduced reaction time in the PVT [F(1.56) = 4.134, p = 0.01, eta 2 = 0.181] and increased the number of correct responses in the DMS [F(1.56) = 4.690, p = 0.005, eta 2 = 0.201], demonstrating a significant enhancing effect of LLLT and EX on cognitive performance. LLLT + EX effects were similar but showed no significantly greater improvement on PVT and DMS than LLLT or EX alone. The transcranial infrared laser stimulation and acute aerobic exercise treatments were similarly effective for cognitive enhancement, suggesting that they augment prefrontal cognitive functions similarly.

Lasers Med Sci 2016 May 25

https://www.ncbi.nlm.nih.gov/pubmed/?term=27220529

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Multi-watt near-infrared light therapy as a neuroregenerative treatment for traumatic brain injury.

Henderson TA

Neuro-Laser Foundation, The Synaptic Space, Neuro-Luminance, Centennial, CO, USA..

Neural Regen Res 2016 Apr 11(4) 563-5

https://www.ncbi.nlm.nih.gov/pubmed/?term=27212912

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A Novel Method to Promote Behavioral Improvement and Enhance Mitochondrial Function Following An Embolic Stroke.

Lapchak PA, Boitano PD

Director of Translational Research, Cedars-Sinai Medical Center Department of Neurology & Neurosurgery, Advanced Health Sciences Pavilion 8305, 127 S. San Vicente Blvd, Los Angeles 90048, United States. Electronic address: paul.lapchak@cshs.org. Cedars-Sinai Medical Center, Department of Neurology, Advanced Health Sciences Pavilion 8220, 127 S. San Vicente Blvd, Los Angeles 90048, United States. Electronic address: paul.boitano@cshs.org..

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for stroke; tPA increases cerebral reperfusion, blood flow and improved behavior. Novel transcranial laser therapy (TLT) also enhances cerebral blood flow and activates mitochondrial function. Using the rabbit small clot embolic stroke model (RSCEM), we studied the effects of continuous wave TLT (7.5mW/cm2) alone or in combination with standardized intravenous (IV) tPA (3.3mg/kg) applied 1 hour post-embolization on 3 endpoints: 1) behavioral function measured 2 days [effective stroke dose (P50 in mg) producing neurological deficits in 50% of embolized rabbits], 2) intracerebral hemorrhage (ICH) rate, and 3) cortical adenosine-5′-triphosphate (ATP) content was measured 6 hours following embolization. TLT and tPA significantly (p<0.05) increased P50 values by 95% and 56% (p<0.05), respectively over control. TLT-tPA increased P50 by 136% over control (p<0.05). Embolization reduced cortical ATP content by 39%; decreases that were attenuated by either TLT or tPA treatment (p<0.05). TLT-tPA further enhanced cortical ATP levels 22% above that measured in naive control. TLT and tPA both effectively and safely, without affecting ICH rate, improved behavioral outcome in embolized rabbits; and there was a trend (p>0.05) for the TLT-tPA combination to further increase P50. TLT and tPA both attenuated stroke-induced ATP deficits, and the combination of tPA and TLT produced an additive effect on ATP levels. This study demonstrates that the combination of TLT-tPA enhances ATP production, and suggests that tPA-induced reperfusion in combination with TLT neuroprotection therapy may optimally protect viable cells in the cortex measured using ATP levels as a marker.

Brain Res 2016 May 11

https://www.ncbi.nlm.nih.gov/pubmed/?term=27180104

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Laser acupuncture as an adjunctive therapy for spastic cerebral palsy in children.

Dabbous OA , Mostafa YM , El Noamany HA , El Shennawy SA , El Bagoury MA

Department of Medical Applications of Laser, National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza, Egypt. oladabous@yahoo.com. Department of Medical Applications of Laser, National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza, Egypt. Department of Neurosurgery, Faculty of medicine, Menofyia University, Shebin El Kom, Egypt. Department of Pediatric Physical Therapy, Faculty of Physical Therapy, Cairo University, Giza, Egypt. Department of Pediatric Physical Therapy, Faculty of Physical Therapy, Pharos University, Alexandria, Egypt..

Laser acupuncture is widely used as an alternative line of treatment in several chronic pediatric diseases. To investigate whether biostimulation by low-level laser on acupuncture points adds a clinical benefit to conventional physiotherapy in hemiplegic spastic cerebral palsy (CP) children. Forty spastic hemiplegic cerebral palsy children by age 1-4 years were chosen from the pediatric outpatient clinic of the National Institute of Laser Enhanced Sciences (NILES), Cairo University, and Menofyia University hospitals. They were randomly divided into control and study groups; 20 children each. Both groups received physiotherapy for 3 months, while only the study group also received laser acupuncture (low-level laser 650 nm with 50 mW power was applied at each acupoint for 30 s giving an energy density of 1.8 J/cm2). Preassessment and postassessment of muscle tone, the range of motion (ROM), and gross motor function measurements (GMFMs) were obtained, and the results were statistically analyzed. Comparison between posttreatment measures for the control vs. study groups showed significant difference in muscle tone (wrist flexors and plantar flexors) in favor of the study group, while range of motion showed no significant differences. GMFM showed no significant difference in total score while there was a significant difference in goal total score (sum of % scores for each dimension identified as goal area divided by number of goal areas) in favor of the study group. Laser acupuncture has a beneficial effect on reducing spasticity in spastic cerebral palsy and may be helpful in improving their movement.

Lasers Med Sci 2016 May 4

https://www.ncbi.nlm.nih.gov/pubmed/?term=27147077

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Errata: Transcranial low-level laser therapy (810 nm) temporarily inhibits peripheral nociception: photoneuromodulation of glutamate receptors, prostatic acid phophatase, and adenosine triphosphate.

Pires de Sousa MV , Ferraresi C , Kawakubo M , Kaippert B , Yoshimura EM , Hamblin MR

Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; University of Sao Paulo, Institute of Physics, Laboratory of Radiation Dosimetry and Medical Physics, Rua do Matao, Travessa R, 187, Cidade Universitaria, Sao Paulo, Brazil; Bright Photomedicine Ltd., CIETEC Building, 2242 Lineu Prestes, Sao Paulo 05508-000, Brazil. Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; Federal University of Sao Carlos, Department of Physical Therapy, Laboratory of Electro-Thermo-Phototherapy, Street Washington Luis, km 235. Monjolinho, Sao Carlos, Sao Paulo 13565-905, Brazil; Federal University of Sao Carlos, Post-Graduation Program in Biotechnology, Street Washington Luis, km 235. Monjolinho, Sao Carlos, Sao Paulo 13560-000, Brazil; University of Sao Paulo, Optics Group, Physics Institute of Sao Carlos, Street Miguel Petroni, 146-Jardim Bandeirantes, Sao Carlos, Sao Paulo 13560-970, Brazil. Massachusetts General Hospital , Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States. Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; Federal University of Rio de Janeiro, Carlos Chagas Filho, 373-Cidade Universitaria, Rio de Janeiro, RJ 21941-170, Brazil. University of Sao Paulo , Institute of Physics, Laboratory of Radiation Dosimetry and Medical Physics, Rua do Matao, Travessa R, 187, Cidade Universitaria, Sao Paulo, Brazil. Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Dermatology, 50 Staniford Street #807, Boston, Massachusetts 02114, United States; Harvard-MIT, Division of Health Sciences and Technology, 77 Massachusetts Avenue, E25-518, Cambridge, Massachusetts 02139, United States..

[This corrects the article DOI: 10.1117/1.NPh.3.1.015003.].

Neurophotonics 2016 Jan 3(1) 019801

https://www.ncbi.nlm.nih.gov/pubmed/?term=27115021

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Glaucoma: Focus on mitochondria in relation to pathogenesis and neuroprotection.

Osborne NN , Nunez-Alvarez C , Joglar B , Del Olmo-Aguado S

Fundacion de Investigacion Oftalmologica, Avda. Doctores Fernandez-Vega 34, E-33012 Oviedo, Asturias, Spain. Electronic address: Neville.osborne@eye.ox.ac.uk. Fundacion de Investigacion Oftalmologica, Avda. Doctores Fernandez-Vega 34, E-33012 Oviedo, Asturias, Spain. Fundacion de Investigacion Oftalmologica, Avda. Doctores Fernandez-Vega 34, E-33012 Oviedo, Asturias, Spain. Fundacion de Investigacion Oftalmologica, Avda. Doctores Fernandez-Vega 34, E-33012 Oviedo, Asturias, Spain..

Primary open-angle glaucoma (POAG) is a common form of glaucoma in which retinal ganglion cells (RGCs) die at varying intervals. Primary open-angle glaucoma is often associated with an increased intraocular pressure (IOP), which when reduced, can slow down the progression of the disease. However, it is essential to develop better modes of treatments for glaucoma patients. In this overview, we discuss the hypothesis that RGC mitochondria are affected during the initiation of POAG, by becoming gradually weakened, but at different rates because of their specific receptor profiles. With this in mind, we argue that neuroprotection in the context of glaucoma should focus on preserving RGC mitochondrial function and suggest a number of ways by which this can theoretically be achieved. Since POAG is a chronic disease, any neuroprotective treatment strategy must be tolerated over many years. Theoretically, topically applied substances should have the fewest side effects, but it is questionable whether sufficient compounds can reach RGC mitochondria to be effective. Therefore, other delivery procedures that might result in greater concentrations of neuroprotectants reaching RGC mitochondria are being developed. Red-light therapy represents another therapeutic alternative for enhancing RGC mitochondrial functions and has the advantage of being both non-toxic and non-invasive.

Eur J Pharmacol 2016 Apr 14

https://www.ncbi.nlm.nih.gov/pubmed/?term=27090928

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Non-invasive brain stimulation to promote alertness and awareness in chronic patients with disorders of consciousness: Low-level, near-infrared laser stimulation vs. focused shock wave therapy.

Werner C , Byhahn M , Hesse S

Medical Park Berlin Humboldtmuhle, Neurologische Rehabilitation, Charite – Universitatsmedizin Berlin, Germany. Haus Havelblick, Department for intensive care nursing, Havelschanze, Berlin, Germany. Medical Park Berlin Humboldtmuhle, Neurologische Rehabilitation, Charite – Universitatsmedizin Berlin, Germany..

PURPOSE: In order to promote alertness and awareness in patients with severe disorders of consciousness (DOC) frontal near infrared laser stimulation (N-LT) or transcranial focused shock wave therapy (F-SWT) might be an option. The study compared both techniques in severe chronic DOC patients. METHODS: Sixteen DOC patients were allocated to two groups (A and B). A three week baseline either followed a frontal N-LT (0,1 mJ/mm2, 10 min per session), five times a week over four weeks (group A), or a F-SWT (0,1 mJ/mm2, 4000 stimuli per session) three times a week over four weeks (group B). The primary variable was the revised Coma Recovery Scale (r-CRS, 0-23), blindly assessed. RESULTS: Both groups improved in the r-CRS over time, but revealed no differences between groups. One patient of group B had a focal seizure in the third therapy week. One patient with akinetic mutism improved most and three patients with global hypoxia did not improve at all. CONCLUSIONS: Both options might be an option to increase alertness and awareness of chronic DOC patients. An akinetic mutism seems to be a positive and severe cerebral hypoxia a negative predictor. Epileptic seizures are a potential unwanted side effect. More clinical studies are warranted.

Restor Neurol Neurosci 2016 Apr 11

https://www.ncbi.nlm.nih.gov/pubmed/?term=27080072

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[Restoration of the complicated locomotor functions of the upper extremities in the patients surviving ischemic stroke].

Bondarenko FV , Makarova MR , Turova EA

State autonomous healthcare facility “Moscow Research and Practical Centre for Medical Rehabilitation, Restorative and Sports Medicine”, Moscow Health Department, Moscow, Russia, 105120. State autonomous healthcare facility “Moscow Research and Practical Centre for Medical Rehabilitation, Restorative and Sports Medicine”, Moscow Health Department, Moscow, Russia, 105120. State autonomous healthcare facility “Moscow Research and Practical Centre for Medical Rehabilitation, Restorative and Sports Medicine”, Moscow Health Department, Moscow, Russia, 105120..

During the late and residual periods of stroke, it is necessary to pay attention to the training of complex spatial movements along with the traditional restoration of the balance and strength of para-articular muscles and the mobility of the paretic limb joints. The objective of the present study was to evaluate the effectiveness of robotic therapy for the recovery of the functions of the upper extremities in the late and residual periods of stroke. The study involved 52 patients who had survived ischemic stroke in the middle cerebral artery. The patients were divided randomly into 2 groups. All of them performed therapeutic physical exercises based on the standard technique during 5 days a week for 3 weeks. In addition, the treatment included massage, laser and pulsed current therapy. The patients of the main group (n=36) were additionally trained to perform complex spatial movements with special emphasis on their speed, fluidity, precision, and agility with the use of the Multi Joint System (MJS) robotic electromechanical device (40 min, 5 days/wk x 3wk). The analysis of the results of the study has demonstrated the statistically significant difference in the degree of improvement of the range of motion (ROM) in the elbow and shoulder joints, the speed and the accuracy of these movements between the patients of the main and control groups. It is concluded that the instrumental restoration of complex spatial movements of the upper extremities during the late and residual periods of stroke contributes not only to the improvement of the functional capabilities but also to the enhancement of independence and personal adjustment of the stroke patients.

Vopr Kurortol Fizioter Lech Fiz Kult 2016 Jan-Feb 93(1) 11-5

https://www.ncbi.nlm.nih.gov/pubmed/?term=27030562

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Repeated transcranial low-level laser therapy for traumatic brain injury in mice: biphasic dose response and long-term treatment outcome.

Xuan W, Huang L, Hamblin MR

Dept of Otorhinolaryngology, Head and Neck Surgery, Ruikang Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, China. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Hamblin@helix.mgh.harvard.edu. Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA. Hamblin@helix.mgh.harvard.edu. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Hamblin@helix.mgh.harvard.edu..

We previously showed that near-infrared laser photobiomodulation (PBM) (810 nm, CW, 18 J/cm2 , 25 mW/cm2 ) delivered to the mouse daily for 3-days after a controlled cortical impact traumatic brain injury (TBI) gave a significant improvement in neurological/cognitive function. However the same parameters delivered 14X daily gave significantly less benefit. This biphasic dose response intrigued us, and we decided to follow the mice that received 3X or 14X laser treatments out to 56-days post-TBI. We found the 14X group showed worse neurological function than the no-treatment TBI group at 2-weeks, but started to improve steadily during the next 6-weeks, and by 56-days were significantly better than the no-treatment TBI mice, but still worse than the 3X mice. A marker of activated glial cells (GFAP) was significantly increased in the brain regions (compared to both untreated TBI and 3X groups) at 4-weeks in the 14X group, but the GFAP had fallen to low levels in both 3X and 14X groups by 8-weeks. We conclude that an excessive number of laser-treatments delivered to mice can temporarily inhibit the process of brain repair stimulated by tPBM, but then the inhibitory effect ceases, and brain repair can resume. The mechanism may be temporary induction of reactive gliosis.

J Biophotonics 2016 Mar 15

https://www.ncbi.nlm.nih.gov/pubmed/?term=26990361

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Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

Cassano P, Petrie SR, Hamblin MR, Henderson TA, Iosifescu DV

Massachusetts General Hospital, Depression Clinical and Research Program, One Bowdoin Square, 6th Floor, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Psychiatry, 401 Park Drive, Boston, Massachusetts 02215, United States. Massachusetts General Hospital, Depression Clinical and Research Program, One Bowdoin Square, 6th Floor, Boston, Massachusetts 02114, United States. Massachusetts General Hospital, Wellman Center for Photomedicine, 50 Blossom Street, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Dermatology, 55 Fruit Street, Boston, Massachusetts 02114, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. Synaptic Space, 3979 East Arapahoe Road, Littleton, Colorado 80122, United States; Neuro-Laser Foundation, Suite 420, 215 South Wadsworth, Lakewood, Colorado 80226, United States. Mount Sinai Medical School, Mood and Anxiety Disorders Program, 1428 Madison Avenue, New York, New York 10029, United States; Mount Sinai Medical School, Department of Psychiatry and Neuroscience, 1 Gustave L. Levy Place, New York, New York 10029, United States..

We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: “near-infrared radiation,” “NIR,” “low-level light therapy,” “low-level laser therapy,” or “LLLT” plus “depression.” We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

Neurophotonics 2016 Jul 3(3) 031404

https://www.ncbi.nlm.nih.gov/pubmed/?term=26989758

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Pre-conditioning with transcranial low-level light therapy reduces neuroinflammation and protects blood-brain barrier after focal cerebral ischemia in mice.

Lee HI, Park JH, Park MY, Kim NG, Park KJ, Choi BT, Shin YI, Kyoung Shin H

Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Medical Research Center of Color Seven, Seoul, Republic of Korea. Medical Research Center of Color Seven, Seoul, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Research Institute for Convergence of Biomedical Science and Technology, Pusan National UniversityYangsan Hospital, Yangsan, Gyeongnam, Republic of Korea. Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Gyeongnam, Republic of Korea. Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea..

PURPOSE: Transcranial low-level light therapy (LLLT) has gained interest as a non-invasive, inexpensive and safe method of modulating neurological and psychological functions in recent years. This study was designed to examine the preventive effects of LLLT via visible light source against cerebral ischemia at the behavioral, structural and neurochemical levels. METHODS: The mice received LLLT twice a day for 2 days prior to photothrombotic cortical ischemia. RESULTS: LLLT significantly reduced infarct size and edema and improved neurological and motor function 24 h after ischemic injury. In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was accompanied by a reduction in the expression of inflammatory mediators and inhibition of MAPK activation and NF-kappaB translocation in the ischemic cortex. Concomitantly, LLLT significantly attenuated leukocyte accumulation and infiltration into the infarct perifocal region. LLLT also prevented BBB disruption after ischemic events, as indicated by a reduction of Evans blue leakage and water content. These findings were corroborated by immunofluorescence staining of the tight junction-related proteins in the ischemic cortex in response to LLLT. CONCLUSIONS: Non-invasive intervention of LLLT in ischemic brain injury may provide a significant functional benefit with an underlying mechanism possibly being suppression of neuroinflammation and reduction of BBB disruption.

Restor Neurol Neurosci 2016 Jan 30

https://www.ncbi.nlm.nih.gov/pubmed/?term=26889965

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Evaluation of low-level laser therapy in the treatment of masticatory muscles spasticity in children with cerebral palsy.

Santos MT, Diniz MB, Gouw-Soares SC, Lopes-Martins RA, Frigo L, Baeder FM

Cruzeiro do Sul University, Institute of Dentistry, Rua Galvao Bueno 868, Liberdade, Sao Paulo, SP CEP 01506-000, Brazil. Cruzeiro do Sul University, Institute of Dentistry, Rua Galvao Bueno 868, Liberdade, Sao Paulo, SP CEP 01506-000, Brazil. Sao Paulo University (USP), School of Dentistry, Especial Laboratory of Lasers in Dentistry (LELO), Av. Prof. Lineu Prestes, 2227 Cidade Universitaria, Sao Paulo, SP CEP 05508-900, Brazil. Mogi das Cruzes University (UMC), Biomedical Engineering Research and Post-Graduate Center, Av. Dr. Candido Xavier de Almeida e Souza 200, Mogi das Cruzes, SP CEP 08780-911, Brazil. Cruzeiro do Sul University, Institute of Dentistry, Rua Galvao Bueno 868, Liberdade, Sao Paulo, SP CEP 01506-000, Brazil. Cruzeiro do Sul University, Institute of Dentistry, Rua Galvao Bueno 868, Liberdade, Sao Paulo, SP CEP 01506-000, Brazil..

J Biomed Opt 2016 Feb 1 21(2) 28001

https://www.ncbi.nlm.nih.gov/pubmed/?term=26882450

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Near-infrared light (670 nm) reduces MPTP-induced parkinsonism within a broad therapeutic time window.

Reinhart F, El Massri N, Johnstone DM, Stone J, Mitrofanis J, Benabid AL, Moro C

CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble Alpes, 38000, Grenoble, France. florian.reinhart@cea.fr. Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. nabil.elmassri@sydney.edu.au. Department of Physiology F13, University of Sydney, Sydney, 2006, Australia. daniel.johnstone@sydney.edu.au. Department of Physiology F13, University of Sydney, Sydney, 2006, Australia. jonathan.stone@sydney.edu.au. Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia. john.mitrofanis@sydney.edu.au. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble Alpes, 38000, Grenoble, France. alimlouis@sfr.fr. CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble Alpes, 38000, Grenoble, France. cecile.moro@cea.fr..

We have shown previously that near-infrared light (NIr), when applied at the same time as a parkinsonian insult (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP), reduces behavioural deficits and offers neuroprotection. Here, we explored whether the timing of NIr intervention-either before, at the same time or after the MPTP insult-was important. Mice received MPTP injections (total of 50 mg/kg) and, at various stages in relation to these injections, extracranial application of NIr. Locomotor activity was tested with an open-field test, and brains were processed for immunohistochemistry. Our results showed that regardless of when NIr was applied in relation to MPTP insult, behavioural impairment was reduced by a similar magnitude. The beneficial effect of NIr was fast-acting (within minutes) and long-lasting (for several days). There were more dopaminergic cells in the NIr-treated MPTP groups than in the MPTP group; there was no clear indication that a particular combination of NIr treatment and MPTP injection resulted in a higher cell number. In summary, irrespective of whether it was applied before, at the same time as or after MPTP insult, NIr reduced both behavioural and structural measures of damage by a similar magnitude. There was a broad therapeutic time window of NIr application in relation to the stage of toxic insult, and the NIr was fast-acting and long-lasting.

Exp Brain Res 2016 Feb 15

https://www.ncbi.nlm.nih.gov/pubmed/?term=26879772

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Neuroprotective Effects Against POCD by Photobiomodulation: Evidence from Assembly/Disassembly of the Cytoskeleton.

Liebert AD, Chow RT, Bicknell BT, Varigos E

University of Sydney, Sydney, NSW, Australia. Brain and Mind Institute, University of Sydney, Sydney, NSW, Australia. Australian Catholic University, Sydney, NSW, Australia. Olympic Park Clinic, Melbourne, VIC, Australia..

Postoperative cognitive dysfunction (POCD) is a decline in memory following anaesthesia and surgery in elderly patients. While often reversible, it consumes medical resources, compromises patient well-being, and possibly accelerates progression into Alzheimer’s disease. Anesthetics have been implicated in POCD, as has neuroinflammation, as indicated by cytokine inflammatory markers. Photobiomodulation (PBM) is an effective treatment for a number of conditions, including inflammation. PBM also has a direct effect on microtubule disassembly in neurons with the formation of small, reversible varicosities, which cause neural blockade and alleviation of pain symptoms. This mimics endogenously formed varicosities that are neuroprotective against damage, toxins, and the formation of larger, destructive varicosities and focal swellings. It is proposed that PBM may be effective as a preconditioning treatment against POCD; similar to the PBM treatment, protective and abscopal effects that have been demonstrated in experimental models of macular degeneration, neurological, and cardiac conditions.

J Exp Neurosci 2016 10 1-19

https://www.ncbi.nlm.nih.gov/pubmed/?term=26848276

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Transcranial low-level laser therapy (810 nm) temporarily inhibits peripheral nociception: photoneuromodulation of glutamate receptors, prostatic acid phophatase, and adenosine triphosphate.

Pires de Sousa MV, Ferraresi C, Kawakubo M, Kaippert B, Yoshimura EM, Hamblin MR

Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; University of Sao Paulo, Institute of Physics, Laboratory of Radiation Dosimetry and Medical Physics, Rua do Matao, Travessa R, 187, Cidade Universitaria, Sao Paulo, Brazil; Bright Photomedicine Ltd., CIETEC Building, 2242 Lineu Prestes, Sao Paulo 05508-000, Brazil. Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; Federal University of Sao Carlos, Department of Physical Therapy, Laboratory of Electro-Thermo-Phototherapy, Street Washington Luis, km 235. Monjolinho, Sao Carlos, Sao Paulo 13565-905, Brazil; Federal University of Sao Carlos, Post-Graduation Program in Biotechnology, Street Washington Luis, km 235. Monjolinho, Sao Carlos, Sao Paulo 13560-000, Brazil; University of Sao Paulo, Optics Group, Physics Institute of Sao Carlos, Street Miguel Petroni, 146-Jardim Bandeirantes, Sao Carlos, Sao Paulo 13560-970, Brazil. Massachusetts General Hospital , Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States. Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; Federal University of Rio de Janeiro, Carlos Chagas Filho, 373-Cidade Universitaria, Rio de Janeiro, RJ 21941-170, Brazil. University of Sao Paulo , Institute of Physics, Laboratory of Radiation Dosimetry and Medical Physics, Rua do Matao, Travessa R, 187, Cidade Universitaria, Sao Paulo, Brazil. Massachusetts General Hospital, Wellman Center for Photomedicine, BAR414, 40 Blossom Street, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Dermatology, 50 Staniford Street #807, Boston, Massachusetts 02114, United States; Harvard-MIT, Division of Health Sciences and Technology, 77 Massachusetts Avenue, E25-518, Cambridge, Massachusetts 02139, United States..

Photobiomodulation or low-level light therapy has been shown to attenuate both acute and chronic pain, but the mechanism of action is not well understood. In most cases, the light is applied to the painful area, but in the present study we applied light to the head. We found that transcranial laser therapy (TLT) applied to mouse head with specific parameters (810 nm laser, [Formula: see text], 7.2 or [Formula: see text]) decreased the reaction to pain in the foot evoked either by pressure (von Frey filaments), cold, or inflammation (formalin injection) or in the tail (evoked by heat). The pain threshold increasing is maximum around 2 h after TLT, remains up to 6 h, and is finished 24 h after TLT. The mechanisms were investigated by quantification of adenosine triphosphate (ATP), immunofluorescence, and hematoxylin and eosin (H&E) staining of brain tissues. TLT increased ATP and prostatic acid phosphatase (an endogenous analgesic) and reduced the amount of glutamate receptor (mediating a neurotransmitter responsible for conducting nociceptive information). There was no change in the concentration of tubulin, a constituent of the cytoskeleton, and the H&E staining revealed no tissue damage. This is the first study to show inhibition of peripheral pain due to photobiomodulation of the central nervous system.

Neurophotonics 2016 Jan 3(1) 015003

https://www.ncbi.nlm.nih.gov/pubmed/?term=26835486

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Transcranial laser stimulation improves human cerebral oxygenation.

Tian F, Hase SN, Gonzalez-Lima F, Liu H

Department of Bioengineering, University of Texas, Arlington, Texas, 76010. Department of Bioengineering, University of Texas, Arlington, Texas, 76010. Department of Psychology and Institute for Neuroscience, University of Texas, Austin, Texas, 78712. Department of Bioengineering, University of Texas, Arlington, Texas, 76010..

BACKGROUND AND OBJECTIVE: Transcranial laser stimulation of the brain with near-infrared light is a novel form of non-invasive photobiomodulation or low-level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near-infrared spectroscopy (fNIRS). MATERIALS AND METHODS: Two separate experiments were conducted in which 1,064-nm laser stimulation was administered at (1) the center and (2) the right side of the forehead, respectively. The laser emitted at a power of 3.4 W and in an area of 13.6 cm2 , corresponding to 0.25 W/cm2 irradiance. Stimulation duration was 10 minutes. Nine healthy male and female human participants of any ethnic background, in an age range of 18-40 years old were included in each experiment. RESULTS: In both experiments, transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration (Delta[HbO2 ]) and a decrease of deoxygenated hemoglobin concentration (Delta[Hb]) in both cerebral hemispheres. Improvements in cerebral oxygenation were indicated by a significant increase of differential hemoglobin concentration (Delta[HbD] = Delta[HbO2 ] – Delta[Hb]). These effects increased in a dose-dependent manner over time during laser stimulation (10 minutes) and persisted after laser stimulation (6 minutes). The total hemoglobin concentration (Delta[HbT] = Delta[HbO2] + Delta[Hb]) remained nearly unchanged in most cases. CONCLUSION: Near-infrared laser stimulation applied to the forehead can transcranially improve cerebral oxygenation in healthy humans. Lasers Surg. Med. (c) 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Lasers Surg Med 2016 Jan 12

https://www.ncbi.nlm.nih.gov/pubmed/?term=26817446

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Corrigendum to “Low-Level Laser Stimulation on Adipose-Tissue-Derived Stem Cell Treatments for Focal Cerebral Ischemia in Rats”.

Shen CC, Yang YC, Chiao MT, Chan SC, Liu BS

Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Physical Therapy, Hung Kuang University, Taichung 43302, Taiwan; Department of Medicine, National Defense Medical Center, Taipei 114, Taiwan; Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan. Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan..

[This corrects the article DOI: 10.1155/2013/594906.].

Evid Based Complement Alternat Med 2015 2015 278951

https://www.ncbi.nlm.nih.gov/pubmed/?term=26798396

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Turning On Lights to Stop Neurodegeneration: The Potential of Near Infrared Light Therapy in Alzheimer’s and Parkinson’s Disease.

Johnstone DM, Moro C, Stone J, Benabid AL, Mitrofanis J

Department of Physiology, University of Sydney Sydney, NSW, Australia. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus Grenoble, France. Department of Physiology, University of Sydney Sydney, NSW, Australia. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus Grenoble, France. University Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus Grenoble, France..

Alzheimer’s and Parkinson’s disease are the two most common neurodegenerative disorders. They develop after a progressive death of many neurons in the brain. Although therapies are available to treat the signs and symptoms of both diseases, the progression of neuronal death remains relentless, and it has proved difficult to slow or stop. Hence, there is a need to develop neuroprotective or disease-modifying treatments that stabilize this degeneration. Red to infrared light therapy (lambda = 600-1070 nm), and in particular light in the near infrared (NIr) range, is emerging as a safe and effective therapy that is capable of arresting neuronal death. Previous studies have used NIr to treat tissue stressed by hypoxia, toxic insult, genetic mutation and mitochondrial dysfunction with much success. Here we propose NIr therapy as a neuroprotective or disease-modifying treatment for Alzheimer’s and Parkinson’s patients.

Front Neurosci 2015 9 500

https://www.ncbi.nlm.nih.gov/pubmed/?term=26793049

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Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.

Reinhart F, Massri NE, Chabrol C, Cretallaz C, Johnstone DM, Torres N, Darlot F, Costecalde T, Stone J, Mitrofanis J, Benabid AL, Moro C

CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and Physiology, University of Sydney, New South Wales, Australia. .

OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson’s disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other “symptomatic” elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.

J Neurosurg 2015 Nov 27 1-13

https://www.ncbi.nlm.nih.gov/pubmed/?term=26613166

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SPECT Perfusion Imaging Demonstrates Improvement of Traumatic Brain Injury With Transcranial Near-infrared Laser Phototherapy.

Henderson TA, Morries LD

Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. Near-infrared (NIR) light has shown benefits in animal models and human trials for stroke and in animal models for TBI. Diodes emitting low-level NIR often have lacked therapeutic efficacy, perhaps failing to deliver sufficient radiant energy to the necessary depth. In this case report, a patient with moderate TBI documented in anatomical magnetic resonance imaging (MRI) and perfusion single-photon emission computed tomography (SPECT) received 20 NIR treatments in the course of 2 mo using a high-power NIR laser. Symptoms were monitored by clinical examination and a novel patient diary system specifically designed for this patient population. Clinical application of these levels of infrared energy for this patient with TBI yielded highly favorable outcomes with decreased depression, anxiety, headache, and insomnia, whereas cognition and quality of life improved. Neurological function appeared to improve based on changes in the SPECT by quantitative analysis. NIR in the power range of 10-15 W at 810 and 980 nm can safely and effectively treat chronic symptoms of TBI.

Adv Mind Body Med 2015 Fall 29(4) 27-33

https://www.ncbi.nlm.nih.gov/pubmed/?term=26535475

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Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury.

Peplow PV

Department of Anatomy, University of Otago, Dunedin, New Zealand..

At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints.

Neural Regen Res 2015 Aug 10(8) 1186-90

https://www.ncbi.nlm.nih.gov/pubmed/?term=26487831

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Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson’s Disease.

Oueslati A, Lovisa B, Perrin J, Wagnieres G, van den Bergh H, Tardy Y, Lashuel HA

Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland; Centre de Recherche du Centre Hospitalier de Quebec, Axe Neuroscience et Departement de Medecine Moleculaire de l’Universite Laval, Quebec, G1V4G2, Canada. Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland; Medos International Sarl, a Johnson&Johnson company, Chemin Blanc 38, CH-2400, Le Locle, Switzerland. Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland. Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland. Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland. Medos International Sarl, a Johnson&Johnson company, Chemin Blanc 38, CH-2400, Le Locle, Switzerland. Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), CH-1015, Lausanne, Switzerland; Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, P.O. Box 5825, Doha, Qatar..

Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human alpha-synuclein (alpha-syn) in the substantia nigra of an AAV-based rat genetic model of Parkinson’s disease (PD). In this model, daily exposure of both sides of the rat’s head to 808-nm near-infrared light for 28 consecutive days alleviated alpha-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies.

PLoS One 2015 10(10) e0140880

https://www.ncbi.nlm.nih.gov/pubmed/?term=26484876

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Transcranial Near-Infrared Laser Therapy for Stroke: How to Recover from Futility in the NEST-3 Clinical Trial.

Lapchak PA, Boitano PD

Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center (CSMC), 127 S. San Vicente Blvd. Suite 8305, Los Angeles, CA, 90048, USA. Paul.Lapchak@cshs.org. Department of Neurology, Cedars-Sinai Medical Center (CSMC), 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA..

Development of drugs and devices for the treatment of stroke is not exempt from current translational research standards, which include Stroke Treatment Academic Industry Roundtable (STAIR) criteria and RIGOR guidelines. Near-infrared laser therapy (NILT) was developed to treat stroke in an era when STAIR criteria were not adhered to, thus NILT was not optimized in multiple species, nor was it optimized for efficacy across barriers in translational animal models before proceeding to expensive and extensive clinical trials. Moreover, the majority of rodent studies did not adhere to RIGOR guidelines. This ultimately led to failure in the NeuroThera Effectiveness and Safety Trial-3. Because NILT remains a promising therapeutic approach to treat stroke, we designed a systematic study to determine laser light penetration profiles across the skull of four different species with increasing skull thickness: mouse, rat, rabbit, and human.Our study demonstrates that NILT differentially penetrates the skulls. There is especially extensive attenuation of light energy penetration across the human calvaria, compared with animal skulls, which suggests that the power density setting used in stroke clinical trials may not have optimally stimulated neuroprotection and repair pathways. The results of our study suggest that NILT cannot be sufficiently optimized in “small” animals and directly translated to humans because of significant variances of skull thickness and penetration characteristics across species. NILT neuroprotection should be further studied using a research design that endeavors to incorporate human skull characteristics (thickness) into the development plan to increase the probability of success in stroke victims.

Acta Neurochir Suppl 2016 121 7-12

https://www.ncbi.nlm.nih.gov/pubmed/?term=26463915

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Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study.

Cassano P, Cusin C, Mischoulon D, Hamblin MR, De Taboada L, Pisoni A, Chang T, Yeung A, Ionescu DF, Petrie SR, Nierenberg AA, Fava M, Iosifescu DV

Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. LiteCure LLC, Newark, DE 19702, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. Depression Clinical & Research Program, Massachusetts General Hospital, Boston, MA 02114, USA ; Department of Psychiatry, The Mount Sinai Hospital, New York, NY 10029, USA..

Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 +/- 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm(2) and a fluence of 84 J/cm(2) for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 +/- 4.4 (SD) to 13 +/- 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199.

Psychiatry J 2015 2015 352979

https://www.ncbi.nlm.nih.gov/pubmed/?term=26356811

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Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy.

Morries LD, Cassano P, Henderson TA

Neuro-Laser Foundation, Lakewood, CO, USA. Harvard Medical School, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA. Neuro-Laser Foundation, Lakewood, CO, USA ; The Synaptic Space, Centennial, CO, USA..

Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. In this review, treatments for the chronic TBI patient are discussed, including pharmaceuticals, nutraceuticals, cognitive therapy, and hyperbaric oxygen therapy. All available literature suggests a marginal benefit with prolonged treatment courses. An emerging modality of treatment is near-infrared (NIR) light, which has benefit in animal models of stroke, spinal cord injury, optic nerve injury, and TBI, and in human trials for stroke and TBI. The extant literature is confounded by variable degrees of efficacy and a bewildering array of treatment parameters. Some data indicate that diodes emitting low-level NIR energy often have failed to demonstrate therapeutic efficacy, perhaps due to failing to deliver sufficient radiant energy to the necessary depth. As part of this review, we present a retrospective case series using high-power NIR laser phototherapy with a Class IV laser to treat TBI. We demonstrate greater clinical efficacy with higher fluence, in contrast to the bimodal model of efficacy previously proposed. In ten patients with chronic TBI (average time since injury 9.3 years) given ten treatments over the course of 2 months using a high-power NIR laser (13.2 W/0.89 cm(2) at 810 nm or 9 W/0.89 cm(2) at 810 nm and 980 nm), symptoms of headache, sleep disturbance, cognition, mood dysregulation, anxiety, and irritability improved. Symptoms were monitored by depression scales and a novel patient diary system specifically designed for this study. NIR light in the power range of 10-15 W at 810 nm and 980 nm can safely and effectively treat chronic symptoms of TBI. The clinical benefit and effects of infrared phototherapy on mitochondrial function and secondary molecular events are discussed in the context of adequate radiant energy penetration.

Neuropsychiatr Dis Treat 2015 11 2159-75

https://www.ncbi.nlm.nih.gov/pubmed/?term=26347062

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Near-infrared photonic energy penetration: can infrared phototherapy effectively reach the human brain?

Henderson TA, Morries LD

The Synaptic Space, Centennial, CO, USA ; Neuro-Laser Foundation, Lakewood, CO, USA. Neuro-Laser Foundation, Lakewood, CO, USA..

Traumatic brain injury (TBI) is a growing health concern effecting civilians and military personnel. Research has yielded a better understanding of the pathophysiology of TBI, but effective treatments have not been forthcoming. Near-infrared light (NIR) has shown promise in animal models of both TBI and stroke. Yet, it remains unclear if sufficient photonic energy can be delivered to the human brain to yield a beneficial effect. This paper reviews the pathophysiology of TBI and elaborates the physiological effects of NIR in the context of this pathophysiology. Pertinent aspects of the physical properties of NIR, particularly in regards to its interactions with tissue, provide the background for understanding this critical issue of light penetration through tissue. Our recent tissue studies demonstrate no penetration of low level NIR energy through 2 mm of skin or 3 cm of skull and brain. However, at 10-15 W, 0.45%-2.90% of 810 nm light penetrated 3 cm of tissue. A 15 W 810 nm device (continuous or non-pulsed) NIR delivered 2.9% of the surface power density. Pulsing at 10 Hz reduced the dose of light delivered to the surface by 50%, but 2.4% of the surface energy reached the depth of 3 cm. Approximately 1.22% of the energy of 980 nm light at 10-15 W penetrated to 3 cm. These data are reviewed in the context of the literature on low-power NIR penetration, wherein less than half of 1% of the surface energy could reach a depth of 1 cm. NIR in the power range of 10-15 W at 810 and 980 nm can provide fluence within the range shown to be biologically beneficial at 3 cm depth. A companion paper reviews the clinical data on the treatment of patients with chronic TBI in the context of the current literature.

Neuropsychiatr Dis Treat 2015 11 2191-208

https://www.ncbi.nlm.nih.gov/pubmed/?term=26346298

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Traumatic Brain Injury: A Major Medical Problem That Could Be Treated Using Transcranial, Red/Near-Infrared LED Photobiomodulation.

Naeser MA, Hamblin MR

1 VA Boston Healthcare System , Boston, Massachusetts. 2 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts. 3 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston, Massachusetts. 4 Department of Dermatology, Harvard Medical School , Boston, Massachusetts. 5 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts..

Photomed Laser Surg 2015 Aug 17

https://www.ncbi.nlm.nih.gov/pubmed/?term=26280257

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Rehabilitative Paradigms after Experimental Brain Injury: Relevance to Human Neurotrauma

Bondi CO, Tehranian-DePasquale R, Cheng JP, Monaco CM, Griesbach GS, Kline AE

The goal of this chapter is to describe four relatively non-invasive rehabilitative paradigms that may have clinical relevance following brain injury. Specifically, the benefits and limitations of environmental enrichment, exercise, low-level laser therapy, and constraint-induced movement therapy will be discussed. Timing issues (e.g., best time to initiate treatment as well as duration of treatment) and the advantage of adjunct therapies (i.e., can they further improve functional outcome) will also be discussed. Overall, the literature suggests that each of the aforementioned therapies confer significant behavioral improvement after experimental brain trauma. Hence, we propose that they should be considered for implementation in clinical rehabilitation.

2015

https://www.ncbi.nlm.nih.gov/pubmed/?term=26269889

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Transcranial Near-Infrared Laser Transmission (NILT) Profiles (800 nm): Systematic Comparison in Four Common Research Species.

Lapchak PA, Boitano PD, Butte PV, Fisher DJ, Holscher T, Ley EJ, Nuno M, Voie AH, Rajput PS

Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; Department of Neurosurgery, Cedars-Sinai Medical center, Los Angeles, California, United States of America. Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America. Department of Neurosurgery, Cedars-Sinai Medical center, Los Angeles, California, United States of America. BURL Concepts Inc., San Diego, California, United States of America. BURL Concepts Inc., San Diego, California, United States of America. Department of Surgery, Cedars-Sinai Medical center, Los Angeles, California, United States of America. Department of Neurosurgery, Cedars-Sinai Medical center, Los Angeles, California, United States of America. BURL Concepts Inc., San Diego, California, United States of America. Department of Neurosurgery, Cedars-Sinai Medical center, Los Angeles, California, United States of America..

BACKGROUND AND PURPOSE: Transcranial near-infrared laser therapy (TLT) is a promising and novel method to promote neuroprotection and clinical improvement in both acute and chronic neurodegenerative diseases such as acute ischemic stroke (AIS), traumatic brain injury (TBI), and Alzheimer’s disease (AD) patients based upon efficacy in translational animal models. However, there is limited information in the peer-reviewed literature pertaining to transcranial near-infrared laser transmission (NILT) profiles in various species. Thus, in the present study we systematically evaluated NILT characteristics through the skull of 4 different species: mouse, rat, rabbit and human. RESULTS: Using dehydrated skulls from 3 animal species, using a wavelength of 800nm and a surface power density of 700 mW/cm2, NILT decreased from 40.10% (mouse) to 21.24% (rat) to 11.36% (rabbit) as skull thickness measured at bregma increased from 0.44 mm in mouse to 0.83 mm in rat and then 2.11 mm in rabbit. NILT also significantly increased (p<0.05) when animal skulls were hydrated (i.e. compared to dehydrated); but there was no measurable change in thickness due to hydration. In human calvaria, where mean thickness ranged from 7.19 mm at bregma to 5.91 mm in the parietal skull, only 4.18% and 4.24% of applied near-infrared light was transmitted through the skull. There was a slight (9.2-13.4%), but insignificant effect of hydration state on NILT transmission of human skulls, but there was a significant positive correlation between NILT and thickness at bregma and parietal skull, in both hydrated and dehydrated states. CONCLUSION: This is the first systematic study to demonstrate differential NILT through the skulls of 4 different species; with an inverse relationship between NILT and skull thickness. With animal skulls, transmission profiles are dependent upon the hydration state of the skull, with significantly greater penetration through hydrated skulls compared to dehydrated skulls. Using human skulls, we demonstrate a significant correlation between thickness and penetration, but there was no correlation with skull density. The results suggest that TLT should be optimized in animals using novel approaches incorporating human skull characteristics, because of significant variance of NILT profiles directly related to skull thickness.

PLoS One 2015 10(6) e0127580

https://www.ncbi.nlm.nih.gov/pubmed/?term=26039354

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Improving executive function using transcranial infrared laser stimulation.

Blanco NJ, Maddox WT, Gonzalez-Lima F

Department of Psychology, The University of Texas at Austin, Texas, USA. Institute for Mental Health Research, The University of Texas at Austin, Texas, USA. Department of Psychology, The University of Texas at Austin, Texas, USA. Institute for Mental Health Research, The University of Texas at Austin, Texas, USA. Institute for Neuroscience, The University of Texas at Austin, Texas, USA. Center for Perceptual Systems, The University of Texas at Austin, Texas, USA. Department of Psychology, The University of Texas at Austin, Texas, USA. Institute for Neuroscience, The University of Texas at Austin, Texas, USA. Division of Pharmacology and Toxicology, The University of Texas at Austin, Texas, USA..

Transcranial infrared laser stimulation is a new non-invasive form of low-level light therapy that may have a wide range of neuropsychological applications. It entails using low-power and high-energy-density infrared light from lasers to increase metabolic energy. Preclinical work showed that this intervention can increase cortical metabolic energy, thereby improving frontal cortex-based memory function in rats. Barrett and Gonzalez-Lima (2013, Neuroscience, 230, 13) discovered that transcranial laser stimulation can enhance sustained attention and short-term memory in humans. We extend this line of work to executive function. Specifically, we ask whether transcranial laser stimulation enhances performance in the Wisconsin Card Sorting Task that is considered the gold standard of executive function and is compromised in normal ageing and a number of neuropsychological disorders. We used a laser of a specific wavelength (1,064 nm) that photostimulates cytochrome oxidase – the enzyme catalysing oxygen consumption for metabolic energy production. Increased cytochrome oxidase activity is considered the primary mechanism of action of this intervention. Participants who received laser treatment made fewer errors and showed improved set-shifting ability relative to placebo controls. These results suggest that transcranial laser stimulation improves executive function and may have exciting potential for treating or preventing deficits resulting from neuropsychological disorders or normal ageing.

J Neuropsychol 2015 May 28

https://www.ncbi.nlm.nih.gov/pubmed/?term=26017772

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Low-level light in combination with metabolic modulators for effective therapy of injured brain.

Dong T, Zhang Q, Hamblin MR, Wu MX

Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA..

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue-like injured brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 13 May 2015; doi:10.1038/jcbfm.2015.87.

J Cereb Blood Flow Metab 2015 May 13

https://www.ncbi.nlm.nih.gov/pubmed/?term=25966949

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Transcranial bright light and symptoms of jet lag: a randomized, placebo-controlled trial.

Jurvelin H, Jokelainen J, Takala T

BACKGROUND: Rapid travel over multiple time zones usually results in transient de-synchronization between environmental time and the biological clock of the individual. Common symptoms are increased daytime sleepiness, reduced sleep duration and quality, and performance impairments. Exposure to ocular bright light is known to alleviate jet lag symptoms and facilitate adaptation to a new time zone. Recently, transcranial bright light (TBL) via the ear canals has been shown to have antidepressant, anxiolytic, and psychomotor performance-enhancing effects. In this case we studied whether intermittent TBL exposure can alleviate jet lag symptoms in a randomized, double-blind, placebo-controlled study. METHODS: Intermittent light exposures (4 x 12 min; day 0: 08:00, 10:00, 12:00, 14:00; days 1-6: 10:00, 12:00, 14:00, 16:00) were administered during the 7-d post-travel period after an eastward transatlantic flight. The symptoms of jet lag were measured by the Visual Analog Scale (VAS), the Karolinska Sleepiness Scale (KSS), and the Profile of Mood States (POMS). RESULTS: We found a significant reduction of overall jet lag symptoms (VAS), subjective sleepiness (KSS), and the fatigue, inertia, and forgetfulness subscales of the POMS when comparing the active TBL treatment group (N = 30) to the placebo group (N = 25). For example, the normalized values of VAS in the TBL, but not the placebo, group returned to pre-travel levels by the final post-travel day (6.16 vs. 15.34). DISCUSSION: Results suggest a cumulative effect of TBL, as the effects emerged on post-travel days 3-4. Intermittent TBL seems to alleviate jet lag symptoms.

Aerosp Med Hum Perform 2015 Apr 86(4) 344-50

https://www.ncbi.nlm.nih.gov/pubmed/?term=25945550

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Preliminary results of highly localized plantar irradiation with low incident levels of mid-infrared energy which contributes to the prevention of dementia associated with underlying diabetes mellitus.

Ryotokuji K, Ishimaru K, Kihara K, Nakajima T, Otani S, Namiki Y

Stress-free Therapy Research Center, Ryotokuji University. Stress-free Therapy Research Center, Ryotokuji University. Stress-free Therapy Research Center, Ryotokuji University. Stress-free Therapy Research Center, Ryotokuji University. Stress-free Therapy Research Center, Ryotokuji University. Stress-free Therapy Research Center, Ryotokuji University..

BACKGROUND AND AIMS: The incidence of vascular dementia (VD) and Alzheimer’s disease (AD) has recently increased and the prevention of progression of these diseases is very difficult. RESULTS: The application of pinpoint plantar long-wavelength infrared light irradiation (PP-LILI) to a patient’s sole, at the point where the line drawn between the first and second metatarsal heads intersects with the vertical line from the medial malleolus, was effective in increasing blood flow to the facial artery, elevating high-density lipoprotein cholesterol (HDL-C) levels, and reducing insulin resistance. CONCLUSIONS: We found that these effects of PP-LILI might be helpful for preventing VD and AD, conditions that are becoming a social problem in an aging Japanese society.

Laser Ther 2015 Mar 31 24(1) 27-32

https://www.ncbi.nlm.nih.gov/pubmed/?term=25941422

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532 nm Low-Power Laser Irradiation Facilitates the Migration of GABAergic Neural Stem/Progenitor Cells in Mouse Neocortex.

Fukuzaki Y, Shin H, Kawai HD, Yamanoha B, Kogure S

Department of Bioinformatics, Graduate School of Engineering, Soka University, Hachioji, Tokyo, Japan. Department of Bioinformatics, Graduate School of Engineering, Soka University, Hachioji, Tokyo, Japan. Department of Bioinformatics, Graduate School of Engineering, Soka University, Hachioji, Tokyo, Japan. Department of Environmental Engineering for Symbiosis, Faculty of Engineering, Soka University, Hachioji, Tokyo, Japan. Department of Bioinformatics, Graduate School of Engineering, Soka University, Hachioji, Tokyo, Japan..

BACKGROUND AND OBJECTIVE: Accumulating evidence has shown that low-power laser irradiation (LLI) affects cell proliferation and survival, but little is known about LLI effects on neural stem/progenitor cells (NSPCs). Here we investigate whether transcranial 532 nm LLI affects NSPCs in adult murine neocortex and in neurospheres from embryonic mice. STUDY DESIGN/MATERIALS AND METHODS: We applied 532 nm LLI (Nd:YVO4, CW, 60 mW) on neocortical surface via cranium in adult mice and on cultured cells from embryonic mouse brains in vitro to investigate the proliferation and migration of NSPCs and Akt expression using immunohistochemical assays and Western blotting techniques. RESULTS: In vivo experiments demonstrated that 532 nm LLI significantly facilitated the migration of GABAergic NSPCs that were induced to proliferate in layer 1 by mild ischemia. In vitro experiments using GABAergic NSPCs derived from embryonic day 14 ganglionic eminence demonstrated that 532 nm LLI for 60 min promoted the migration of GAD67-immunopositive NSPCs with a significant increase of Akt expression. Meanwhile, the LLI induced proliferation, but not migration, of NSPCs that give rise to excitatory neurons. CONCLUSION: It is concluded that 532 nm LLI promoted the migration of GABAergic NSPCs into deeper layers of the neocortex in vivo by elevating Akt expression.

PLoS One 2014 10(4) e0123833

https://www.ncbi.nlm.nih.gov/pubmed/?term=25919297

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Red and NIR light dosimetry in the human deep brain.

Pitzschke A, Lovisa B, Seydoux O, Zellweger M, Pfleiderer M, Tardy Y, Wagnieres G

Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering (ISIC), 1015 Lausanne, Switzerland..

Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 x 201 x 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated mueff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

Phys Med Biol 2015 Apr 7 60(7) 2921-37

https://www.ncbi.nlm.nih.gov/pubmed/?term=25789711

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Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue.

Tedford CE, DeLapp S, Jacques S, Anders J

LumiThera, Inc., Poulsbo, Washington, 98370..

BACKGROUND AND OBJECTIVE: Photobiomodulation (PBM) also known as low-level light therapy has been used successfully for the treatment of injury and disease of the nervous system. The use of PBM to treat injury and diseases of the brain requires an in-depth understanding of light propagation through tissues including scalp, skull, meninges, and brain. This study investigated the light penetration gradients in the human cadaver brain using a Transcranial Laser System with a 30 mm diameter beam of 808 nm wavelength light. In addition, the wavelength-dependence of light scatter and absorbance in intraparenchymal brain tissue using 660, 808, and 940 nm wavelengths was investigated. in vivo. Lasers Surg. Med. 47:312-322, 2015. (c) 2015 Wiley Periodicals, Inc. STUDY DESIGN/MATERIAL AND METHODS: Intact human cadaver heads (n = 8) were obtained for measurement of light propagation through the scalp/skull/meninges and into brain tissue. The cadaver heads were sectioned in either the transverse or mid-sagittal. The sectioned head was mounted into a cranial fixture with an 808 nm wavelength laser system illuminating the head from beneath with either pulsed-wave (PW) or continuous-wave (CW) laser light. A linear array of nine isotropic optical fibers on a 5 mm pitch was inserted into the brain tissue along the optical axis of the beam. Light collected from each fiber was delivered to a multichannel power meter. As the array was lowered into the tissue, the power from each probe was recorded at 5 mm increments until the inner aspect of the dura mater was reached. Intraparenchymal light penetration measurements were made by delivering a series of wavelengths (660, 808, and 940 nm) through a separate optical fiber within the array, which was offset from the array line by 5 mm. Local light penetration was determined and compared across the selected wavelengths. RESULTS: Unfixed cadaver brains provide good anatomical localization and reliable measurements of light scatter and penetration in the CNS tissues. Transcranial application of 808 nm wavelength light penetrated the scalp, skull, meninges, and brain to a depth of approximately 40 mm with an effective attenuation coefficient for the system of 2.22 cm(-1) . No differences were observed in the results between the PW and CW laser light. The intraparenchymal studies demonstrated less absorption and scattering for the 808 nm wavelength light compared to the 660 or 940 nm wavelengths. CONCLUSIONS: Transcranial light measurements of unfixed human cadaver brains allowed for determinations of light penetration variables. While unfixed human cadaver studies do not reflect all the conditions seen in the living condition, comparisons of light scatter and penetration and estimates of fluence levels can be used to establish further clinical dosing. The 808 nm wavelength light demonstrated superior CNS tissue penetration. Lasers Surg. Med. 47:???-???, 2015. (c) 2015 Wiley Periodicals, Inc.

Lasers Surg Med 2015 Apr 47(4) 312-22

https://www.ncbi.nlm.nih.gov/pubmed/?term=25772014

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The effect of LLLT on bone metabolism in children with severe cerebral palsy (a secondary publication).

Asagai Y

Department of Orthopedic Surgery, Shinano Handicapped Children’s Hospital..

BACKGROUND AND AIMS: It is said that the average frequency of bone fracture in hospitalized children with severe cerebral palsy (unable to remain seated) is 1% (0.2 to 2.0%). Cerebral palsy patients’ bones are known to be vulnerable to fracture, and refractory bone atrophy may be observed. However, the effect of low level laser therapy (LLLT) on bone density or bone metabolism has not been fully investigated. In recent years, tests for bone density or bone metabolism markers have become available. MATERIAL AND METHODS: In this study, we evaluated changes in bone density and bone metabolism markers in 4 children with severe cerebral palsy who underwent LLLT for an average of 22 days. RESULTS: B-ALP, a marker of ossification, increased 1 month after the start of irradiation in 3 of the 4 subjects and returned to a level close to the pre-irradiation level 2 months after the start of irradiation. In the remaining subjects in whom B-ALP failed to increase, B-ALP had been low before irradiation. Urinary N-terminal telopeptide (NTx) levels, a marker of bone resorption, decreased in 3 of the 4 subjects after the start of irradiation and remained low even 10 months later. Serum NTx levels tended to decrease in 3 of the 4 subjects. The levels of serum NTx/Crea, Deoxy-Pyridinoline (DPd) and DPd/Crea (DPd/Crea) also decreased in 3 of the 4 subjects. Transient decreases in intact parathyroid hormone (PTH) levels were observed in all 4 cases. Changes were particularly apparent in 2 cases: one with high NTx levels, which showed enhanced bone resorption, and one with high PTH levels, probably due to a vitamin D (VitD) deficiency. Although the metacarpal bone density measured by DIP was found to be lower than in normal children, there were no changes due to LLLT. CONCLUSION: These results suggest that LLLT has a positive influence on bone metabolism in that it temporarily increases bone formation and suppresses bone resorption while also tending to improve secondary hyperparathyroidism caused by VitD deficiency. Enhanced bone resorption in the case with high NTx levels was noteworthy, together with marked changes in the case with high PTH levels due to VitD deficiency. These positive influences on bone metabolism merit attention as potential new indications of LLLT.

Laser Ther 2014 Dec 27 23(4) 243-7

https://www.ncbi.nlm.nih.gov/pubmed/?term=25705079

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Did human hairlessness allow natural photobiomodulation 2 million years ago and enable photobiomodulation therapy today? This can explain the rapid expansion of our genus’s brain.

Mathewson I

Retired Medical Practitioner, 42 Bundaleer Rd, Brookfield, Brisbane Q4069, Australia. Electronic address: mathim@matilda.net.au..

Present hypotheses to explain human hairlessness appear to be inadequate because hairlessness is not accompanied by any immediate benefit. A new, testable, hypothesis is advanced to explain our hairlessness based on photobiomodulation research, also known as low-level light therapy. This shows that red and near infrared radiation has a very beneficial effect on superficial tissues, including the brain. Random mutation/s resulting in complete hairlessness allowed early humans to receive daily doses of red and near infrared radiation at sunset. Photobiomodulation research shows this has a twofold effect: it results in increased mitochondrial respiratory chain activity with consequent ATP ‘extrasynthesis’ in all superficial tissues, including the brain. It also advantageously affects the expression of over 100 genes through the activation of transcription factor NFkB which results in cerebral metabolic and haemodynamic enhancement. It is also possible that melanin can supply electrons to the respiratory chain resulting in ATP extrasynthesis. These effects would start automatically as soon as hairlessness occurred resulting in a selective sweep of the mutation/s involved. This was followed by the very rapid brain evolution of the last 2my which, it is suggested, was due to intelligence-led evolution based initially on the increased energy and adeptness of the newly hairless individuals.

Med Hypotheses 2015 May 84(5) 421-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=25703782

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Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial.

Hacke W, Schellinger PD, Albers GW, Bornstein NM, Dahlof BL, Fulton R, Kasner SE, Shuaib A, Richieri SP, Dilly SG, Zivin J, Lees KR

From the Department of Neurology, Heidelberg University, Heidelberg, Germany.

BACKGROUND AND PURPOSE: On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. METHODS: We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated
Stroke 2014 Nov 45(11) 3187-93

https://www.ncbi.nlm.nih.gov/pubmed/?term=25293665

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Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice.

Xuan W, Vatansever F, Huang L, Hamblin MR

Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Department of Otolaryngology, Nanning 530021, ChinabWellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United StatescHarvard Medical School. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United StatescHarvard Medical School, Department of Dermatology, Boston, Massachusetts 02115, United States. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United StatescHarvard Medical School, Department of Dermatology, Boston, Massachusetts 02115, United StatesdGuangxi Medical University, First Affiliated College. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, United StatescHarvard Medical School, Department of Dermatology, Boston, Massachusetts 02115, United StateseHarvard-MIT Division of Health Sciences and Technolo..

The use of transcranial low-level laser (light) therapy (tLLLT) to treat stroke and traumatic brain injury (TBI) is attracting increasing attention. We previously showed that LLLT using an 810-nm laser 4 h after controlled cortical impact (CCI)-TBI in mice could significantly improve the neurological severity score, decrease lesion volume, and reduce Fluoro-Jade staining for degenerating neurons. We obtained some evidence for neurogenesis in the region of the lesion. We now tested the hypothesis that tLLLT can improve performance on the Morris water maze (MWM, learning, and memory) and increase neurogenesis in the hippocampus and subventricular zone (SVZ) after CCI-TBI in mice. One and (to a greater extent) three daily laser treatments commencing 4-h post-TBI improved neurological performance as measured by wire grip and motion test especially at 3 and 4 weeks post-TBI. Improvements in visible and hidden platform latency and probe tests in MWM were seen at 4 weeks. Caspase-3 expression was lower in the lesion region at 4 days post-TBI. Double-stained BrdU-NeuN (neuroprogenitor cells) was increased in the dentate gyrus and SVZ. Increases in double-cortin (DCX) and TUJ-1 were also seen. Our study results suggest that tLLLT may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis.

J Biomed Opt 2014 Oct 19(10) 108003

https://www.ncbi.nlm.nih.gov/pubmed/?term=25292167

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660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

Li X, Hou W, Wu X, Jiang W, Chen H, Xiao N, Zhou P

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China ; Chongqing Engineering Research Center for Medical Electronics Technology, Chongqing, China. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China ; Chongqing Engineering Research Center for Medical Electronics Technology, Chongqing, China. Rehabilitation Center, Children’s Hospital of Chongqing Medical University, Chongqing, China. Chongqing Engineering Research Center for Medical Electronics Technology, Chongqing, China. Rehabilitation Center, Children’s Hospital of Chongqing Medical University, Chongqing, China. Chongqing Engineering Research Center for Medical Electronics Technology, Chongqing, China..

Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2), an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 x 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.

Neural Regen Res 2014 Feb 1 9(3) 236-42

https://www.ncbi.nlm.nih.gov/pubmed/?term=25206807

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Low-level laser therapy for traumatic brain injury in mice increases brain derived neurotrophic factor (BDNF) and synaptogenesis.

Xuan W, Agrawal T, Huang L, Gupta GK, Hamblin MR

Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Department of Otolaryngology, Traditional Chinese Medical University of Guangxi, Nanning, China..

Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm2 at 50 mW/cm2 . Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF) was significantly upregulated by laser treatment in the dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ) but not in the perilesional cortex (lesion) at day 7 but not at day 28. Synapsin-1 (a marker for synaptogenesis, the formation of new connections between existing neurons) was significantly upregulated in lesion and SVZ but not DG, at 28 days but not 7 days. The data suggest that the benefit of LLLT to the brain is partly mediated by stimulation of BDNF production, which may in turn encourage synaptogenesis. Moreover the pleiotropic benefits of BDNF in the brain suggest LLLT may have wider applications to neurodegenerative and psychiatric disorders. Neurological Severity Score (NSS) for TBI mice.

J Biophotonics 2014 Sep 8 9999(9999)

https://www.ncbi.nlm.nih.gov/pubmed/?term=25196192

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Laser Acupuncture at HT7 Acupoint Improves Cognitive Deficit, Neuronal Loss, Oxidative Stress, and Functions of Cholinergic and Dopaminergic Systems in Animal Model of Parkinson’s Disease.

Wattanathorn J, Sutalangka C

Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand ; Integrative Complementary Alternative Medicine Research and Development Center, Khon Kaen University, Khon Kaen 40002, Thailand. Integrative Complementary Alternative Medicine Research and Development Center, Khon Kaen University, Khon Kaen 40002, Thailand ; Department of Physiology, Neuroscience Program, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand..

To date, the therapeutic strategy against cognitive impairment in Parkinson’s disease (PD) is still not in satisfaction level and requires novel effective intervention. Based the oxidative stress reduction and cognitive enhancement induced by laser acupuncture at HT7, the beneficial effect of laser acupuncture at HT7 against cognitive impairment in PD has been focused. In this study, we aimed to determine the effect of laser acupuncture at HT7 on memory impairment, oxidative stress status, and the functions of both cholinergic and dopaminergic systems in hippocampus of animal model of PD. Male Wistar rats, weighing 180-220 g, were induced unilateral lesion at right substantianigra by 6-OHDA and were treated with laser acupuncture continuously at a period of 14 days. The results showed that laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus. The decreased AChE, MAO-B, and MDA together with increased GSH-Px in hippocampus of a 6-OHDA lesion rats were also observed. In conclusion, laser acupuncture at HT7 can improve neuron degeneration and memory impairment in animal model of PD partly via the decreased oxidative stress and the improved cholinergic and dopaminergic functions. More researches concerning effect of treatment duration are still required.

Evid Based Complement Alternat Med 2014 2014 937601

https://www.ncbi.nlm.nih.gov/pubmed/?term=25161693

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Differential Effects of 670 and 830 nm Red near Infrared Irradiation Therapy: A Comparative Study of Optic Nerve Injury, Retinal Degeneration, Traumatic Brain and Spinal Cord Injury.

Giacci MK, Wheeler L, Lovett S, Dishington E, Majda B, Bartlett CA, Thornton E, Harford-Wright E, Leonard A, Vink R, Harvey AR, Provis J, Dunlop SA, Hart NS, Hodgetts S, Natoli R, Van Den Heuvel C, Fitzgerald M

Experimental and Regenerative Neurosciences, The University of Western Australia, Crawley, Australia.

Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.

PLoS One 2014 9(8) e104565

https://www.ncbi.nlm.nih.gov/pubmed/?term=25105800

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Can Phototherapy Ameliorate the Progression of Parkinson’s Disease?

Jang I, Han C

1 Department of Internal Medicine, College of Korean Medicine, Woosuk University , Jeonbuk, Republic of Korea..

Photomed Laser Surg 2014 Aug 5

https://www.ncbi.nlm.nih.gov/pubmed/?term=25093424

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Investigation regarding prevention of insufficiency fractures in children with severe cerebral palsy by Light-Emitting Diode (LED) irradiation.

Asagai Y, Yamamoto K, Ohshiro T, Ohshiro T

Shinano Handicapped Children’s Hospital, Shimosuwa, Nagano, Japan. Department of Orthopaedic Surgery, Tokyo Medical University, Shinjuku, Tokyo, Japan. Japan Medical Laser Laboratory, Shinanomachi,Tokyo, Japan. Ohshiro Clinic, Shinanomachi, Tokyo, Japan..

Bone metabolism in children with severe fractures was examined, risk factors for fractures were characterized, and effects of LED (light-emitting diode) irradiation on the risk factors for fractures were investigated. Since insufficiency fracture in children with severe cerebral palsy can be caused without obvious external force in daily care, it is sometimes handled as a medical accident and can lead to a lawsuit. It is very important to explain the possibility of an insufficiency fracture to guardians before a fracture is caused. However, risk factors for fractures in bone metabolism has not been well investigated and preventive treatment of fractures have also not been established. Risk factors in bone metabolism were investigated in 14 cases of insufficiency fracture in children with severe cerebral palsy accompanied by akathisia in this study. Fractures were likely caused around 8 years old when children grew rapidly, and either IGF-1 or BAP showed low values in all cases. A group with LED irradiation consisting of 25 cases indicated a normal value of IGF-1 related to bone growth, BAP related to bone density and NTX/Cr. A case irradiated to LED for more than one month clearly showed normal bone metabolism compared with the change within a non irradiated group after one year. LED irradiation increased bone density and femur cortical bone thickness, and improved bone age. Adequate effects were not seen in two children at 14 years of age. The commercially available LED light bulbs that we used have a peak at 446-477 nm in the blue wave length, but also have second peaks at 574 nm in green, at 590 nm in yellow, and even 612 nm in orange and 660 nm in red are included. Although it is thought that such a variety of wave lengths might have a good influence on bone metabolism; exposure time and distance, number of regions, and time period irradiated to LED are important factors, since the LED power density is low (0.9 mW/m(2) with a 30 cm distance). Our results suggest that LED irradiation can be a phototherapy to activate human homeostasis.

Laser Ther 2014 Jul 1 23(2) 121-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=25071311

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Low-Level Laser Therapy Ameliorates Disease Progression in a Mouse Model of Alzheimer’s Disease.

Farfara D, Tuby H, Trudler D, Doron-Mandel E, Maltz L, Vassar RJ, Frenkel D, Oron U

Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel..

Low-level laser therapy (LLLT) has been used to treat inflammation, tissue healing, and repair processes. We recently reported that LLLT to the bone marrow (BM) led to proliferation of mesenchymal stem cells (MSCs) and their homing in the ischemic heart suggesting its role in regenerative medicine. The aim of the present study was to investigate the ability of LLLT to stimulate MSCs of autologous BM in order to affect neurological behavior and beta-amyloid burden in progressive stages of Alzheimer’s disease (AD) mouse model. MSCs from wild-type mice stimulated with LLLT showed to increase their ability to maturate towards a monocyte lineage and to increase phagocytosis activity towards soluble amyloid beta (Abeta). Furthermore, weekly LLLT to BM of AD mice for 2 months, starting at 4 months of age (progressive stage of AD), improved cognitive capacity and spatial learning, as compared to sham-treated AD mice. Histology revealed a significant reduction in Abeta brain burden. Our results suggest the use of LLLT as a therapeutic application in progressive stages of AD and imply its role in mediating MSC therapy in brain amyloidogenic diseases.

J Mol Neurosci 2014 Jul 4

https://www.ncbi.nlm.nih.gov/pubmed/?term=24994540

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Expression of mPGES-1 and IP mRNA is reduced by LLLT in both subplantar and brain tissues in the model of peripheral inflammation induced by carrageenan.

Chagas LR, Silva JA Jr, de Almeida Pires J, Costa MS

Instituto de Pesquisa e Desenvolvimento – IP&D, Universidade do Vale do Paraiba – UNIVAP, Av. Shishima Hifumi, 2911. Urbanova, CEP 12244-000, Sao Jose dos Campos, SP, Brazil..

The increase in PGE2 production by microsomal PGE synthase-1 (mPGES-1) in CNS contributes to the severity of the inflammatory and pain responses in the model of edema formation and hyperalgesia induced by carrageenan. PGI2, alike to PGE2, plays an important role in the inflammation. Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and the acute inflammatory process. In this work, we studied the effect of LLLT on the expression of both mPGES-1 and IP messenger RNA (mRNA), in either subplantar or total brain tissues obtained from rats submitted to model of edema formation and hyperalgesia induced by carrageenan administration. The test sample consisted of 30 rats divided into five groups: A1 (control-saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). The animals from groups A3 and A5 were irradiated 1 h after induction of inflammation by carrageenan injection. Continuous-wave red laser with wavelengths of 660 nm and dose of 7.5 J/cm2 was used. Six hours after carrageenan-induced inflammation, mPGES-1 and prostacyclin receptor (IP) mRNA expression were significantly increased both in subplantar and brain tissues. LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar and brain tissues. We suggest that LLLT is able to reduce both inflammation and hyperalgesia observed in the model of edema formation and hyperalgesia induced by carrageenan, by a mechanism involving the decrease in the expression of both mPGES-1 and IP.

Lasers Med Sci 2014 Jun 29

https://www.ncbi.nlm.nih.gov/pubmed/?term=24974175

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Combining neuroprotectants in a model of retinal degeneration: no additive benefit.

Di Marco F, Di Paolo M, Romeo S, Colecchi L, Fiorani L, Spana S, Stone J, Bisti S

Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy. Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy. Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy. Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy. Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy. Discipline of Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia. Discipline of Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia; ARC Centre of Excellence in Vision Science, The Australian National University, Canberra, Australia. Department of Biotechnology and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy; ARC Centre of Excellence in Vision Science, The Australian National University, Canberra, Australia..

The central nervous system undergoing degeneration can be stabilized, and in some models can be restored to function, by neuroprotective treatments. Photobiomodulation (PBM) and dietary saffron are distinctive as neuroprotectants in that they upregulate protective mechanisms, without causing measurable tissue damage. This study reports a first attempt to combine the actions of PBM and saffron. Our working hypothesis was that the actions of PBM and saffron in protecting retinal photoreceptors, in a rat light damage model, would be additive. Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive. Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection. Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.

PLoS One 2014 9(6) e100389

https://www.ncbi.nlm.nih.gov/pubmed/?term=24955576

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[The role of magnetolaserotherapy in the correction of the adaptive potential of the brain in the children suffering absence seizures].

Kravtsova EIu, Kravtsov IuI, Shevchenko KV.

We have conducted a course of magnetic laser therapy targeted on the vegetative structures at the neck of the children suffering absence seizures in an attempt to optimize the functioning of the non-specific brain structures. The study has demonstrated that such treatment promotes normalization of the components of the orientation response to sound almost to the level observed in the healthy children. The alpha-index returned to the normal value as well.

Vopr Kurortol Fizioter Lech Fiz Kult 2014 Mar-Apr (2) 25-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=24864485

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Low-level laser therapy effectively prevents secondary brain injury induced by immediate early responsive gene X-1 deficiency.

Zhang Q, Zhou C, Hamblin MR, Wu MX

1] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA. 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA. 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA [3] Affiliated faculty member of the Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA. 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA [3] Affiliated faculty member of the Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA..

A mild insult to the brain can sometimes trigger secondary brain injury, causing severe postconcussion syndrome, but the underlying mechanism is ill understood. We show here that secondary brain injury occurs consistently in mice lacking immediate early responsive gene X-1 (IEX-1), after a gentle impact to the head, which closely simulates mild traumatic brain injury in humans. The pathologic lesion was characterized by extensive cell death, widespread leukocyte infiltrates, and severe tissue loss. On the contrary, a similar insult did not induce any secondary injury in wild-type mice. Strikingly, noninvasive exposure of the injured head to a low-level laser at 4 hours after injury almost completely prevented the secondary brain injury in IEX-1 knockout mice. The low-level laser therapy (LLLT) suppressed proinflammatory cytokine expression like interleukin (IL)-1beta and IL-6 but upregulated TNF-alpha. Moreover, although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP production and selective modulation of proinflammatory mediators. This new closed head injury model provides an excellent tool to investigate the pathogenesis of secondary brain injury as well as the mechanism underlying the beneficial effect of LLLT.

J Cereb Blood Flow Metab 2014 May 21

https://www.ncbi.nlm.nih.gov/pubmed/?term=24849666

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The Antidepressant Effect of Laser Acupuncture: A Comparison of the Resting Brain’s Default Mode Network in Healthy and Depressed Subjects During Functional Magnetic Resonance Imaging.

Quah-Smith I, Suo C, Williams MA, Sachdev PS

School of Psychiatry, Faculty of Medicine, University of New South Wales (UNSW) , Australia . ; Neuropsychiatric Institute (NPI) , Prince of Wales Hospital, Randwick, Australia . Brain and Ageing Research Program, Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, University of New South Wales , New South Wales, Australia . Macquarie Centre for Cognitive Sciences, Macquarie University , Sydney, Australia . School of Psychiatry, Faculty of Medicine, University of New South Wales (UNSW) , Australia . ; Neuropsychiatric Institute (NPI) , Prince of Wales Hospital, Randwick, Australia . ; Centre for Healthy Brain Ageing, NPI, Euroa Centre, Prince of Wales Hospital , New South Wales, Australia ..

BACKGROUND: It has been suggested that the antidepressant effect of laser acupuncture involves modulation of the default mode network (DMN) or resting state network (RSN). In this study, the authors investigated changes in the DMN during laser acupuncture in depressed and nondepressed participants. OBJECTIVE: To aim of this study was to determine if the modulation of the DMN effects by laser acupuncture in depressed participants are different from those of nondepressed participants. DESIGN: Randomized stimulation was performed with laser acupuncture on four putative antidepressant acupoints (LR 14, LR 8, CV 14, and HT 7) in a block on-off design, while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from each subject’s whole brain on a 3T scanner. DMN patterns of the participants were identified, using an independent component analysis. The identified DMN components from both the nondepressed group and the depressed group were then analytically compared using SPM5. SETTING: This study took place at a research institute. SUBJECTS: Ten nondepressed participants and 10 depressed participants (DS) as confirmed by the Hamilton Depression Rating Scale (HAM-D) participated in this study. INTERVENTION: Low Intensity Laser Acupuncture. MAIN OUTCOME MEASURES: Significant DMN patterns in one group were greater than those in the other group. RESULTS: The nondepressed participants had significant modulation of DMN in the frontal region at the medial frontal gyrus (verum laser>rest, p<0.001) for three acupoints (LR 14, LR 8, and CV 14). For the depressive participants, the DMN modulation occurred at the inferior parietal cortex and the cerebellum (verum laser>rest, p<0.001). CONCLUSIONS: Laser acupuncture on LR 8, LR 14, and CV 14 stimulated both the anterior and posterior DMN in both the nondepressed and depressed participants. However, in the nondepressed participants, there was consistently outstanding modulation of the anterior DMN at the medial frontal gyrus across all three acupoints. In the depressed participants, there was wider posterior DMN modulation at the parieto-temporal-limbic cortices. This is part of the antidepressant effect of laser acupuncture.

Med Acupunct 2013 Apr 25(2) 124-133

https://www.ncbi.nlm.nih.gov/pubmed/?term=24761169

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Augmentation of cognitive brain functions with transcranial lasers.

Gonzalez-Lima F, Barrett DW

Department of Psychology and Institute for Neuroscience, University of Texas at Austin Austin, TX, USA. Department of Psychology and Institute for Neuroscience, University of Texas at Austin Austin, TX, USA..

Front Syst Neurosci 2014 8 36

https://www.ncbi.nlm.nih.gov/pubmed/?term=24672439

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[The early postoperative rehabilitation of the patients presenting with cholelithiasis and experiencing psychoemotional stress].

Poddubnaia OA, Marsheva SI

Early postoperative rehabilitation of the patients presenting with cholelithiasis and experiencing psychoemotional stress is designed to restore the function of bile secretion, enhance their adaptive capabilities, and normalize the psychovegetative status for the purpose of preventing further progress of the disease and reducing the risk of the development of post-cholecystectomy syndrome. The inclusion of drinking mineral water, magnetic laser therapy, and UHF therapy in the combined rehabilitative treatment of such patients results in the appreciable enhancement of all functional abilities of the body manifest as the significant improvement and normalization of clinical and laboratory characteristics (elimination of clinical symptoms of the disease, improvement of general and biochemycal parameters of peripheral blood). Simultaneously, the adaptive capabilities and the psychovegetative status of the patients improved as apparent from the increased lymphocyte count, normalization of the Kerdo and Hildebrandt indices and indices of stress level, decreased psychoemotional stress, enhancement of physical functioning characteristics. Taken together, these changes account for the high effectiveness of the above procedures of early postoperative rehabilitation of the patients presenting with cholelithiasisand experiencing psychoemotional stress (94.7%).

Vopr Kurortol Fizioter Lech Fiz Kult 2013 Nov-Dec (6) 36-41

https://www.ncbi.nlm.nih.gov/pubmed/?term=24640655

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Significant improvements on cognitive performance post- transcranial, red/near-infrared LED treatments in chronic, mild TBI: Open-protocol study.

Naeser MA, Zafonte R, Krengel MH, Martin PI, Frazier J, Hamblin M, Knight JA, Meehan W, Baker EH

VA Boston Healthcare System, 150 So. Huntington Ave., 12-A, Boston, Massachusetts, United States, 02130, 857-364-4030, 617-739-8926, Boston University School of Medicine, Neurology, 85 E. Concord St, Boston, Massachusetts, United States, 02118, 857-364-4030, 617-739-8926 ; mnaeser@bu.edu..

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased ATP important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is non-invasive, painless, and non-thermal (FDA-cleared, non-significant risk device). Eleven chronic, mTBI participants (26-62 Yr, 6M) with non-penetrating head injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (MWF, 6 Wks), starting at 10 Mo to 8 Yr post- mTBI (MVA or sports-related; and one participant, IED blast injury). Four had a history of multiple concussions. Each LED cluster head (2.1″ diameter, 500mW, 22.2mW/cm2) was applied for 10 min to each of 11 scalp placements (13 J/cm2). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre- LED, and at 1 Wk, 1 and 2 Mo post- the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for Stroop test for Executive Function, Trial 3 inhibition (p=.004); Stroop, Trial 4 inhibition switching (p=.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=.003); and CVLT-II, Long Delay Free Recall (p=.006). Participants reported improved sleep, and fewer PTSD symptoms, if present. Participants and family reported better ability to perform social, interpersonal and occupational functions. These open-protocol data suggest placebo controlled studies are warranted.

J Neurotrauma 2014 Feb 25

https://www.ncbi.nlm.nih.gov/pubmed/?term=24568233

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Low-level laser therapy (LLLT) reduces the COX-2 mRNA expression in both subplantar and total brain tissues in the model of peripheral inflammation induced by administration of carrageenan.

Prianti AC Jr, Silva JA Jr, Dos Santos RF, Rosseti IB, Costa MS

Instituto de Pesquisa e Desenvolvimento-IP&D, Universidade do Vale do Paraiba-UNIVAP, Av. Shishima Hifumi 2911, Sao Jose dos Campos, Urbanova, CEP: 12244-000, SP, Brazil..

In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm2, resulting in an energy dosage of 7.5 J/cm2. Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm2) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS.

Lasers Med Sci 2014 Feb 16

https://www.ncbi.nlm.nih.gov/pubmed/?term=24532118

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Non-pharmaceutical therapies for stroke: mechanisms and clinical implications.

Chen F, Qi Z, Luo Y, Hinchliffe T, Ding G, Xia Y, Ji X

Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, Beijing 100053, China. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, Beijing 100053, China. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, Beijing 100053, China. The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA. Shanghai Research Center for Acupuncture and Meridian, Shanghai 201203, China. The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: ying.xia@uth.tmc.edu. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, Beijing 100053, China. Electronic address: jixm@ccmu.edu.cn..

Stroke is deemed a worldwide leading cause of neurological disability and death, however, there is currently no promising pharmacotherapy for acute ischemic stroke aside from intravenous or intra-arterial thrombolysis. Yet because of the narrow therapeutic time window involved, thrombolytic application is very restricted in clinical settings. Accumulating data suggest that non-pharmaceutical therapies for stroke might provide new opportunities for stroke treatment. Here we review recent research progress in the mechanisms and clinical implications of non-pharmaceutical therapies, mainly including neuroprotective approaches such as hypothermia, ischemic/hypoxic conditioning, acupuncture, medical gases and transcranial laser therapy. In addition, we briefly summarize mechanical endovascular recanalization devices and recovery devices for the treatment of the chronic phase of stroke and discuss the relative merits of these devices.

Prog Neurobiol 2014 Apr 115 246-69

https://www.ncbi.nlm.nih.gov/pubmed/?term=24407111

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Photobiomodulation with near infrared light mitigates Alzheimer’s disease-related pathology in cerebral cortex – evidence from two transgenic mouse models.

Purushothuman S, Johnstone DM, Nandasena C, Mitrofanis J, Stone J

Bosch Institute, University of Sydney NSW 2006, Australia. Daniel.Johnstone@sydney.edu.au..

INTRODUCTION: Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer’s disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at an age when substantial pathology is already present in the cerebral cortex. METHODS: We studied two mouse models with AD-related pathologies: the K369I tau transgenic model (K3), engineered to develop neurofibrillary tangles, and the APPswe/PSEN1dE9 transgenic model (APP/PS1), engineered to develop amyloid plaques. Mice were treated with NIr 20 times over a four-week period and histochemistry was used to quantify AD-related pathological hallmarks and other markers of cell damage in the neocortex and hippocampus. RESULTS: In the K3 mice, NIr treatment was associated with a reduction in hyperphosphorylated tau, neurofibrillary tangles and oxidative stress markers (4-hydroxynonenal and 8-hydroxy-2′-deoxyguanosine) to near wildtype levels in the neocortex and hippocampus, and with a restoration of expression of the mitochondrial marker cytochrome c oxidase in surviving neurons. In the APP/PS1 mice, NIr treatment was associated with a reduction in the size and number of amyloid-beta plaques in the neocortex and hippocampus. CONCLUSIONS: Our results, in two transgenic mouse models, suggest that NIr may have potential as an effective, minimally-invasive intervention for mitigating, and even reversing, progressive cerebral degenerations.

Alzheimers Res Ther 2014 Jan 3 6(1) 2

https://www.ncbi.nlm.nih.gov/pubmed/?term=24387311

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Low-level laser stimulation on adipose-tissue-derived stem cell treatments for focal cerebral ischemia in rats.

Shen CC, Yang YC, Chiao MT, Chan SC, Liu BS

Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan ; Department of Physical Therapy, Hung Kuang University, Taichung 43302, Taiwan ; Department of Medicine, National Defense Medical Center, Taipei 114, Taiwan ; Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan. Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan..

This study investigated the effects of large-area irradiation from a low-level laser on the proliferation and differentiation of i-ADSCs in neuronal cells. MTT assays indicated no significant difference between the amount of cells with (LS+) and without (LS-) laser treatment (P > 0.05). However, immunofluorescent staining and western blot analysis results indicated a significant increase in the neural stem-cell marker, nestin, following exposure to low-level laser irradiation (P < 0.05). Furthermore, stem cell implantation was applied to treat rats suffering from stroke. At 28 days posttreatment, the motor functions of the rats treated using i-ADSCs (LS+) did not differ greatly from those in the sham group and HE-stained brain tissue samples exhibited near-complete recovery with nearly no brain tissue damage. However, the motor functions of the rats treated using i-ADSCs (LS-) remained somewhat dysfunctional and tissue displayed necrotic scarring and voids. The western blot analysis also revealed significant expression of oligo-2 in the rats treated using i-ADSCs (LS+) as well as in the sham group (P < 0.05). The results demonstrated that low-level laser irradiation exerts a positive effect on the differentiation of i-ADSCs and can be employed to treat rats suffering from ischemic stroke to regain motor functions.

Evid Based Complement Alternat Med 2013 2013 594906

https://www.ncbi.nlm.nih.gov/pubmed/?term=24363769

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Mitochondrial respiration as a target for neuroprotection and cognitive enhancement.

Gonzalez-Lima F, Barksdale BR, Rojas JC

Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA; Department of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: gonzalezlima@utexas.edu. Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA..

This paper focuses on brain mitochondrial respiration as a therapeutic target for neuroprotection and cognitive enhancement. We propose that improving brain mitochondrial respiration is an important future direction in research and treatment of Alzheimer’s disease (AD) and other conditions associated with cognitive impairment and neurodegeneration. The central thesis is that supporting and improving brain mitochondrial respiration constitutes a promising neurotherapeutic principle, with potential applications in AD as well as in a wide variety of neuropsychological conditions. We propose three different interventional approaches to improve brain mitochondrial respiration based on (a) pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide detailed examples for each type of intervention. First, low-dose USP methylene blue is described as a pharmacological intervention that can successfully increase mitochondrial respiration and result in memory enhancement and neuroprotection. Second, transcranial low-level light/laser therapy with near-infrared light is used to illustrate a photobiomodulation intervention with similar neurometabolic mechanisms of action as low-dose methylene blue. Finally, a nutrition intervention to improve mitochondrial respiration is proposed by increasing ketone bodies in the diet. The evidence discussed for each intervention supports a fundamental neurotherapeutic strategy based on improving oxidative energy metabolism while at the same time reducing the pro-oxidant tendencies of the nervous system. Targeting brain mitochondrial respiration with these three types of interventions is proposed as part of a holistic neurotherapeutic approach to improve brain energy metabolism and antioxidant defenses. This strategy represents a promising new bioenergetics direction for treatment of AD and other neuropsychological disorders featuring cognitive impairment and neurodegeneration.

Biochem Pharmacol 2013 Dec 4

https://www.ncbi.nlm.nih.gov/pubmed/?term=24316434

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Effect of low-level laser stimulation on EEG power in normal subjects with closed eyes.

Wu JH, Chang YC

Department of Biomedical Engineering, Ming Chuan University, No. 5 Deming Road, Guishan Township, Taoyuan County 333, Taiwan..

In a previous study, we found that the low-level laser (LLL) stimulation at the palm with a frequency of 10 Hz was able to induce significant brain activation in normal subjects with opened eyes. However, the electroencephalography (EEG) changes to LLL stimulation in subjects with closed eyes have not been studied. In the present study, the laser array stimulator was applied to deliver insensible laser stimulations to the palm of the tested subjects with closed eyes (the laser group). The EEG activities before, during, and after the laser stimulation were collected. The EEG amplitude powers of each EEG frequency band at 19 locations were calculated. These power data were then analyzed by SPSS software using repeated-measure ANOVAs and appropriate posthoc tests. We found a pronounced decrease in the EEG power in alpha-bandwidth during laser simulation and then less decrease in the EEG power in delta-bandwidth in normal subjects with laser stimulation. The EEG power in beta-bandwidth in the right occipital area also decreased significantly in the laser group. We suggest that LLL stimulation might be conducive to falling into sleep in patients with sleep problems.

Evid Based Complement Alternat Med 2013 2013 476565

https://www.ncbi.nlm.nih.gov/pubmed/?term=24288562

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Comparison between Trans-Cranial Electromagnetic Stimulation and Low-Level Laser on Modulation of Trigeminal Neuralgia.

Seada YI, Nofel R, Sayed HM

Department of Physical Therapy for Neuromuscular Disorders and its Surgery, Faculty of Physical Therapy, Cairo University..

[Purpose] To determine which of the transcranial electromagnetic stimulation or low level laser therapy is more effective in the treatment of trigeminal neuralgia of multiple sclerosis patients. [Methods] Thirty multiple sclerosis patients of both sexes participated in this study. The age of the subjects ranged from 40 to 60 years and their mean age was (56.4-6.6). Participants were randomly selected from Dental and Neurology Outpatient Clinics at King Khalid Hospital, Najran University, Saudi Arabia. Patients were randomly divided into two equal groups of 15. The Laser group received a low level laser therapy, 830 nm wavelength, 10 Hz and 15 min duration, while the Electromagnetic group received repetitive transcranial electromagnetic stimulation at a frequency of 10 Hz, intensity of 50 mA and duration of 20 minutes. Patients were assessed pre and post treatment for degree of pain using a numerical rating scale, maximal oral mouth opening using a digital calibrated caliper, masseter muscle tension using a tensiometer and a compound action potentials of masseter and temporalis muscles. [Results] There were significant improvements after treatment in both groups, with a significant difference between the Electromagnetic and Laser groups, in favor of the Electromagnetic group. [Conclusion] Repetitive transcranial electromagnetic stimulation at 10 Hz, 50 mA, and 20 minutes duration is more effective than low level laser therapy at reducing trigeminal pain, increasing maximum oral mouth opening, masseter and temporalis muscle tension in multiple sclerosis patients.

J Phys Ther Sci 2013 Aug 25(8) 911-914

https://www.ncbi.nlm.nih.gov/pubmed/?term=24259883

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Layer-specific modulation of neuronal excitability by 660-nm laser irradiation in mouse neocortex.

Kumazaki K, Mieda T, Kogure S, Kawai H

Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo, 192-8577, Japan..

It has been reported that laser light irradiation (LLI) could regulate neuronal activities in the forebrain, but little is known if and how LLI in the red wavelength range affects neuronal excitability. Here, we investigated the effects of a continuous diode laser at 660 nm on intrinsic membrane properties and excitability of presumed pyramidal neurons in the thalamocortical input layer (layer 3/4) and in layer 5 of mouse primary auditory cortex using the whole-cell patch-clamp recording technique. In layer 3/4 neurons, 660-nm laser irradiation (LLI-660) at 20 mW for 5 min gradually increased resting membrane potentials, which reached a plateau after irradiation. Concomitantly, LLI-660 decreased onset latency of first action potentials (spikes) without changing spike threshold or peak amplitude, but increased inter-spike interval of initial bursting spike doublets and their peak amplitude ratio. None of these changes was observed in layer 5 neurons. Instead, LLI-660 at 20 mW rapidly reduced spike width ~5 % within 1 min of irradiation onset. The magnitude of this reduction did not change during 5 or 10 min irradiation, and returned quickly to at least baseline levels after turning the LLI off. Decreasing laser power to 10 mW reduced spike width to a lesser extent, suggesting laser power dependence of this phenomenon. These data suggest that LLI-660 regulates different aspects of neuronal excitability in cortical neurons in a layer-dependent manner possibly by affecting different voltage-gated ion channels.

Lasers Med Sci 2013 Nov 14

https://www.ncbi.nlm.nih.gov/pubmed/?term=24232863

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Nanoparticle-emitted light attenuates amyloid-beta-induced superoxide and inflammation in astrocytes.

Bungart BL, Dong L, Sobek D, Sun GY, Yao G, Lee JC

Department of Biological Engineering, University of Missouri, Columbia, MO..

Alzheimer’s disease (AD) is the sixth leading cause of age-related death with no effective intervention yet available. Our previous studies have demonstrated the potential efficacy of Low Level Laser Therapy (LLLT) in AD cell models by mitigating amyloid-beta peptide (Abeta)-induced oxidative stress and inflammation. However, the penetration depth of light is still the major challenge for implementing LLLT in animal models and in the clinical settings. In this study, we present the potential of applying Bioluminescence Resonance Energy Transfer to Quantum Dots (BRET-Qdots) as an alternative near infrared (NIR) light source for LLLT. Our results show that BRET-Qdot-emitted NIR suppresses Abeta-induced oxidative stress and inflammatory responses in primary rat astrocytes. These data provide a proof of concept for a nanomedicine platform for LLLT.

Nanomedicine 2013 Nov 4

https://www.ncbi.nlm.nih.gov/pubmed/?term=24200521

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Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice.

Moro C, Massri NE, Torres N, Ratel D, De Jaeger X, Chabrol C, Perraut F, Bourgerette A, Berger M, Purushothuman S, Johnstone D, Stone J, Mitrofanis J, Benabid AL

CEA-Leti, Grenoble, France; and..

Object Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to the brain, from inside the brain, NIr to the brain. They developed a novel internal surgical device that delivers the NIr to brain regions very close to target damaged or diseased cells. They suggest that this device will be useful in applying NIr within the large human brain, particularly if the target cells have a very deep location. Methods An optical fiber linked to an LED or laser device was surgically implanted into the lateral ventricle of BALB/c mice or Sprague-Dawley rats. The authors explored the feasibility of the internal device, measured the NIr signal through living tissue, looked for evidence of toxicity at doses higher than those required for neuroprotection, and confirmed the neuroprotective effect of NIr on dopaminergic cells in the substantia nigra pars compacta (SNc) in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson disease in mice. Results The device was stable in freely moving animals, and the NIr filled the cranial cavity. Measurements showed that the NIr intensity declined as distance from the source increased across the brain (65% per mm) but was detectable up to 10 mm away. At neuroprotective (0.16 mW) and much higher (67 mW) intensities, the NIr caused no observable behavioral deficits, nor was there evidence of tissue necrosis at the fiber tip, where radiation was most intense. Finally, the intracranially delivered NIr protected SNc cells against MPTP insult; there were consistently more dopaminergic cells in MPTP-treated mice irradiated with NIr than in those that were not irradiated. Conclusions In summary, the authors showed that NIr can be applied intracranially, does not have toxic side effects, and is neuroprotective.

J Neurosurg 2013 Oct 25

https://www.ncbi.nlm.nih.gov/pubmed/?term=24160475

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Laser acupuncture improves memory impairment in an animal model of Alzheimer’s disease.

Sutalangka C, Wattanathorn J, Muchimapura S, Thukham-Mee W, Wannanon P, Tong-Un T

Department of Physiology (Neuroscience Program), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Integrative Complementary Alternative Medicine Research and Development Group, Khon Kaen University, Khon Kaen, Thailand..

The burden of Alzheimer’s disease is continually rising globally, especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. Because the effect of acupuncture at HT7 can improve learning and memory, the beneficial effect of laser acupuncture, a noninvasive form of acupuncture, at HT7 on memory improvement in patients with Alzheimer’s disease has been a focus of research. To elucidate this issue, we used AF64A, a cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180-220 g. Then, the animals were treated with laser acupuncture either at HT7 or at a sham acupoint once daily for 10 minutes for a period of 14 days. Spatial memory assessments were performed at 1, 7, and 14 days after AF64A administration and at the end of the experiment, and the changes in the malondialdehyde (MDA) level and in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded. The results showed that laser acupuncture significantly suppressed AChE activity in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities, no reduction in MDA level in this area was observed. Therefore, laser acupuncture at HT7 is a potential strategy to attenuate memory impairment in patients with Alzheimer’s disease. However, further research, especially on the toxicity of laser acupuncture following repetitive exposure, is essential.

J Acupunct Meridian Stud 2013 Oct 6(5) 247-51

https://www.ncbi.nlm.nih.gov/pubmed/?term=24139462

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Transcranial application of near-infrared low-level laser can modulate cortical excitability.

Konstantinovic LM, Jelic MB, Jeremic A, Stevanovic VB, Milanovic SD, Filipovic SR

Department of Rehabilitation, Faculty of Medicine, University of Belgrade, 11000, Belgrade, Serbia; Klinika za Rehabilitaciju “Dr Miroslav Zotovic”, 11000, Belgrade, Serbia..

BACKGROUND AND OBJECTIVE: Near-infrared low-level laser (NIR-LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS). METHODS: TLS was applied for 5 minutes over the representation of the right first dorsal interosseal muscle (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at baseline and up to 30 minutes after the TLS. RESULTS: The average MEP size was significantly reduced during the first 20 minutes following the TLS. The pattern was present in 10 (71.5%) of the participants. The MEP size reduction correlated negatively with the motor threshold at rest. CONCLUSIONS: TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated cortex. These findings give further insights into the mechanisms of TLS effects in the human cerebral cortex, paving the way for potential applications of TLS in treatment of stroke and in other clinical settings. Lasers Surg. Med. (c) 2013 Wiley Periodicals, Inc.

Lasers Surg Med 2013 Oct 17

https://www.ncbi.nlm.nih.gov/pubmed/?term=24136303

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The time course of action of two neuroprotectants, dietary saffron and photobiomodulation, assessed in the rat retina.

Marco FD, Romeo S, Nandasena C, Purushothuman S, Adams C, Bisti S, Stone J

Department of Biotechnology and Applied Clinical Science, University of L’Aquila Italy..

BACKGROUND: Dietary saffron and photobiomodulation (low-level infrared radiation, PBM) are emerging as therapeutically promising protectants for neurodegenerative conditions, such as the retinal dystrophies. In animal models, saffron and PBM, given in limited daily doses, protect retina and brain from toxin- or light-induced stress. This study addresses the rate at which saffron and PBM, given in daily doses, induce neuroprotection, using a light damage model of photoreceptor degeneration in Sprague Dawley (SD) rats. RESULTS: Rats were raised in dim cyclic (12 h 5 lux, 12 h dark) illumination, treated with saffron or PBM for 2-10 d, and then exposed to bright damaging light (1,000 lux for 24 h). After 1 week survival, the retina was assessed for photoreceptor death (using the TUNEL reaction), for surviving photoreceptor damage (thickness of the outer nuclear layer) and for the expression of a stress-related protein GFAP, using immunohistochemistry. Preconditioning the retina with saffron or PBM reduced photoreceptor death, preserved the population of surviving photoreceptors and reduced the upregulation of GFAP in Muller cells. At the daily dose of saffron used (1 mg/kg), protection was detectable at 2 d, increasing to 10 d. At the daily dose of PBM used (5 J/cm(2) at 670 nm) protection was detectable at 5 d, increasing to 7-10 d. CONCLUSIONS: The results provide time parameters for exploration of the mechanisms and durability of the protection provided by saffron and PBM.

Am J Neurodegener Dis 2013 2(3) 208-20

https://www.ncbi.nlm.nih.gov/pubmed/?term=24093084

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The impact of near-infrared light on dopaminergic cell survival in a transgenic mouse model of parkinsonism.

Purushothuman S, Nandasena C, Johnstone DM, Stone J, Mitrofanis J

Discipline of Physiology, University of Sydney, Australia; Bosch Institute, University of Sydney, Australia..

We have examined whether near-infrared light (NIr) treatment mitigates oxidative stress and increased expression of hyperphosphorylated tau in a tau transgenic mouse strain (K3) that has a progressive degeneration of dopaminergic cells in the substantia nigra pars compacta (SNc). The brains of wild-type (WT), untreated K3 and NIr-treated K3 mice, aged five months (thus after the onset of parkinsonian signs and neuropathology), were labelled immunohistochemically for the oxidative stress markers 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHDG), hyperphosphorylated tau (using the AT8 antibody) and tyrosine hydroxylase (TH). The average intensity and area of 4-HNE, 8-OHDG and AT8 immunoreactivity were measured using the MetaMorph software and TH+ cell number was estimated using stereology. Our results showed immunoreactivity for 4-HNE, 8-OHDG and AT8 within the SNc was increased in K3 mice compared to WT, and that this increase was mitigated by NIr. Results further showed that TH+ cell number was lower in K3 mice than in WT, and that this loss was mitigated by NIr. In summary, NIr treatment reduced the oxidative stress caused by the tau transgene in the SNc of K3 mice and saved SNc cells from degeneration. Our results, when taken together with those in other models, strengthen the notion that NIr treatment saves dopaminergic cells in the parkinsonian condition.

Brain Res 2013 Oct 16 1535C 61-70

https://www.ncbi.nlm.nih.gov/pubmed/?term=23998985

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Low-Level Laser Therapy Rescues Dendrite Atrophy via Upregulating BDNF Expression: Implications for Alzheimer’s Disease.

Meng C, He Z, Xing D

MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China..

Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer’s disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via upregulation of BDNF in both Abeta-treated hippocampal neurons and cultured APP/PS1 mouse hippocampal neurons. Photoactivation of transcription factor CRE-binding protein (CREB) increased both BDNF mRNA and protein expression, since knockdown CREB blocked the effects of LLLT. Furthermore, CREB-regulated transcription was in an ERK-dependent manner. Inhibition of ERK attenuated the DNA-binding efficiency of CREB to BDNF promoter. In addition, dendrite growth was improved after LLLT, characterized by upregulation of Rac1 activity and PSD-95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT by activation of ERK/CREB pathway can ameliorate Abeta-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Abeta-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of AD.

J Neurosci 2013 Aug 14 33(33) 13505-17

https://www.ncbi.nlm.nih.gov/pubmed/?term=23946409

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Thermal Effects of Transcranial Near-Infrared Laser Irradiation on Rabbit Cortex.

Chen Y, De Taboada L, O’Connor M, Delapp S, Zivin JA

University of California San Diego, Department of Neuroscience, 9500 Gilman Drive MTF321, La Jolla, CA 92093-0624. Electronic address: jzivin@ucsd.edu..

BACKGROUND AND PURPOSE: Transcranial near-infrared laser therapy (TLT) improves stroke outcome in animal models. Adequate laser doses are necessary to exert therapeutic effects. However, applying higher laser energy may cause cortical tissue heating and exacerbate stroke injury. The objective of this study is to examine the thermal effect and safety of transcranial near-infrared laser therapy. METHODS: Diode laser with a wavelength of 808nm was used to deliver different power densities to the brain cortex of rabbits. Cortical temperature was monitored and measured using a thermal probe during the 2min transcranial laser irradiation. Neuro-pathological changes were examined with histological staining 24hrs after laser treatment. RESULTS: Transcranial laser irradiation for 2min at cortical power densities of 22.2 and 55.6 mW/cm2 with continuous wave (CW) did not increase cortical temperature in rabbits. With the same treatment regime, cortical power density at 111.1 mW/cm2 increased brain temperature gradually by 0.5 degrees C over the 2min exposure and returned to baseline values within 1-2min post-irradiation. Separately, histological staining was evaluated after triple laser exposure of 22.2 mW/cm2 CW and 111.1 mW/cm2 pulse wave (PW) and showed normal neural cell morphology. CONCLUSIONS: The present study demonstrated that the TLT powers currently utilized in animal stroke studies do not cause cortical tissue heating and histopathological damage.

Neurosci Lett 2013 Aug 7

https://www.ncbi.nlm.nih.gov/pubmed/?term=23933199

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Differential brain effects of laser and needle acupuncture at LR8 using functional MRI.

Quah-Smith I, Williams MA, Lundeberg T, Suo C, Sachdev P

School of Psychiatry, University of New South Wales and Neuropsychiatric Institute (NPI), Prince of Wales Hospital, , Sydney, New South Wales, Australia..

OBJECTIVE: While needle acupuncture is a well-accepted technique, laser acupuncture is being increasingly used in clinical practice. The differential effects of the two techniques are of interest. We examine this in relation to brain effects of activation of LR8, a putative acupuncture point for depression, using functional MRI (fMRI). METHODS: Sixteen healthy participants were randomised to receive low intensity laser acupuncture to LR8 on one side and needle acupuncture to the contralateral LR8. Stimulation was in an on-off block design and brain patterns were recorded under fMRI. RESULTS: Significant activation occurred in the left precuneus during laser acupuncture compared with needle acupuncture and significant activation occurred in the left precentral gyrus during needle acupuncture compared with laser acupuncture. CONCLUSIONS: Laser and needle acupuncture at LR8 in healthy participants produced different brain patterns. Laser acupuncture activated the precuneus relevant to mood in the posterior default mode network while needle acupuncture activated the parietal cortical region associated with the primary motor cortex. Further investigations are warranted to evaluate the clinical relevance of these effects.

Acupunct Med 2013 Sep 31(3) 282-9

https://www.ncbi.nlm.nih.gov/pubmed/?term=23920052

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Neurological and psychological applications of transcranial lasers and LEDs.

Rojas JC, Gonzalez-Lima F

Departments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, Texas 78712, USA; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA..

Transcranial brain stimulation with low-level light/laser therapy (LLLT) is the use of directional low-power and high-fluency monochromatic or quasimonochromatic light from lasers or LEDs in the red-to-near-infrared wavelengths to modulate a neurobiological function or induce a neurotherapeutic effect in a nondestructive and non-thermal manner. The mechanism of action of LLLT is based on photon energy absorption by cytochrome oxidase, the terminal enzyme in the mitochondrial respiratory chain. Cytochrome oxidase has a key role in neuronal physiology, as it serves as an interface between oxidative energy metabolism and cell survival signaling pathways. Cytochrome oxidase is an ideal target for cognitive enhancement, as its expression reflects the changes in metabolic capacity underlying higher-order brain functions. This review provides an update on new findings on the neurotherapeutic applications of LLLT. The photochemical mechanisms supporting its cognitive-enhancing and brain-stimulatory effects in animal models and humans are discussed. LLLT is a potential non-invasive treatment for cognitive impairment and other deficits associated with chronic neurological conditions, such as large vessel and lacunar hypoperfusion or neurodegeneration. Brain photobiomodulation with LLLT is paralleled by pharmacological effects of low-dose USP methylene blue, a non-photic electron donor with the ability to stimulate cytochrome oxidase activity, redox and free radical processes. Both interventions provide neuroprotection and cognitive enhancement by facilitating mitochondrial respiration, with hormetic dose-response effects and brain region activational specificity. This evidence supports enhancement of mitochondrial respiratory function as a generalizable therapeutic principle relevant to highly adaptable systems that are exquisitely sensitive to energy availability such as the nervous system.

Biochem Pharmacol 2013 Jun 24

https://www.ncbi.nlm.nih.gov/pubmed/?term=23806754

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Near-infrared spectroscopy for objectifying cerebral effects of laser acupuncture in term and preterm neonates.

Raith W, Pichler G, Sapetschnig I, Avian A, Sommer C, Baik N, Koestenberger M, Schmolzer GM, Urlesberger B

Division of Neonatology, Department of Paediatrics, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria ; Research Group for Paediatric Traditional Chinese Medicine, TCM Research Centre Graz (Acupuncture Research), Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria..

Laser acupuncture (LA) becomes more and more relevant in neonates and infants. With near-infrared spectroscopy (NIRS), a continuous and noninvasive measurement of tissue oxygenation is possible. Aim was to investigate, whether the application of LA was associated with any changes in regional cerebral oxygen saturation (rcSO2) in term and preterm neonates. The study included 20 neonates (12 males, 8 females). The Large Intestine 4 acupuncture point (LI 4, Hegu) was stimulated by a microlaser needle (10 mW, 685 nm laser needle EG GmbH, Germany) for 5 minutes, bilaterally. All neonates underwent polygraphic recording during undisturbed daytime sleep, including heart rate (HR), peripheral oxygen saturation (SpO2), and measurement of nasal flow. Using NIRS, rcSO2 was measured continuously. Cerebral fractional tissue oxygen extraction (cFTOE) was calculated. We did not observe any significant changes in SpO2 and HR values during the whole observation period. However, there was a significant decrease in rcSO2 (P = 0.003) within postintervention period, accompanied by a significant increase in cFTOE (P = 0.010) in postintervention period.

Evid Based Complement Alternat Med 2013 2013 346852

https://www.ncbi.nlm.nih.gov/pubmed/?term=23762122

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Transcranial Laser Therapy and Infarct Volume.

Kasner SE, Rose DZ, Skokan A, Walker MG, Shi J, Streeter J

Department of Neurology, University of Pennsylvania, Philadelphia, PA..

BACKGROUND AND PURPOSE: Two randomized trials suggested that transcranial laser therapy (TLT) may benefit patients with acute ischemic stroke, although efficacy has not been confirmed. Supportive proof of concept could be demonstrated if TLT reduces the volume of cortical infarction. METHODS: The NeuroThera Efficacy and Safety Trial-2 (NEST-2) was a randomized trial of TLT versus sham in patients with acute ischemic stroke treated within 24 hours of onset. Infarct volumes were measured quantitatively and semiquantitatively on all protocol-required computed tomography (or MRI, if clinically indicated) scans performed on day 5 (+/-2). Two approaches assessed treatment effects on cortex: (1) indirectly, by analyzing total infarct volume among patients with clinical presentations suggesting cortical involvement; and (2) directly, by assessing the cortical Alberta Stroke Program Early CT Score (cASPECTS) components (M1-M6, anterior, posterior) on a 0- to 8-point modified scale. RESULTS: A total of 640 subjects had scans (576 computed tomography, 64 MRI) on day 5. The reliability of ASPECTS (intraclass correlation coefficient=0.85) and cASPECTS (intraclass correlation coefficient=0.82) was excellent, and total ASPECTS was correlated with total infarct volume (r=0.71). In the overall study population, there was no impact of TLT on total infarct volume (P=0.30), total ASPECTS (P=0.85), or cASPECTS (P=0.89). Similarly, no effect was seen in any of the following prespecified subgroups selected to indicate cortical involvement: baseline National Institutes of Health Stroke Scale score >10, Oxfordshire Total Anterior Circulation Syndrome, subjects with aphasia or extinction at baseline, or subjects with radiographic involvement of cortex. CONCLUSIONS: TLT was not associated with a reduction in overall or cortical infarct volume as measured on computed tomography in the subacute phase.

Stroke 2013 May 9

https://www.ncbi.nlm.nih.gov/pubmed/?term=23660846

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[Possibilities of magnetic-laser therapy in comprehensive treatment of patients with brain concussion in acute period].

Zubkova OV, Samosiuk IZ, Polishchuk OV, Shul’ga NM, Samosiuk NI.

The efficacy of magnetic-laser therapy used according to the method developed by us was studied in patients having the brain concussion (BC) in an acute period. The study was based on the dynamics of values of the evoked vestibular potentials and the disease clinical course. It was shown that following the magnetic-laser therapy in combination with traditional pharmacotherapy in BC acute period, the statistically significant positive changes were registered in the quantitative characteristics of the evoked vestibular brain potentials that correlated with the dynamics of the disease clinical course. The data obtained substantiate the possibility of using the magnetic-laser therapy in patients with a mild craniocereblal injury in an acute period.

Lik Sprava 2012 Jul-Sep (5) 106-11

https://www.ncbi.nlm.nih.gov/pubmed/?term=23534278

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Photobiomodulation preserves behaviour and midbrain dopaminergic cells from MPTP toxicity: evidence from two mouse strains.

Moro C, Torres N, El Massri N, Ratel D, Johnstone DM, Stone J, Mitrofanis J, Benabid AL

BACKGROUND: We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Balb/c albino mice, a well-known model for Parkinson’s disease. The present study explores whether NIr treatment offers neuroprotection to these cells in C57BL/6 pigmented mice. In addition, we examine whether NIr influences behavioural activity in both strains after MPTP treatment. We tested for various locomotive parameters in an open-field test, namely velocity, high mobility and immobility. RESULTS: Balb/c (albino) and C57BL/6 (pigmented) mice received injections of MPTP (total of 50 mg/kg) or saline and NIr treatments (or not) over 48 hours. After each injection and/or NIr treatment, the locomotor activity of the mice was tested. After six days survival, brains were processed for TH (tyrosine hydroxylase) immunochemistry and the number of TH+ cells in the substantia nigra pars compacta (SNc) was estimated using stereology. Results showed higher numbers of TH+ cells in the MPTP-NIr groups of both strains, compared to the MPTP groups, with the protection greater in the Balb/c mice (30% vs 20%). The behavioural tests revealed strain differences also. For Balb/c mice, the MPTP-NIr group showed greater preservation of locomotor activity than the MPTP group. Behavioural preservation was less evident in the C57BL/6 strain however, with little effect of NIr being recorded in the MPTP-treated cases of this strain. Finally, there were differences between the two strains in terms of NIr penetration across the skin and fur. Our measurements indicated that NIr penetration was considerably less in the pigmented C57BL/6, compared to the albino Balb/c mice. CONCLUSIONS: In summary, our results revealed the neuroprotective benefits of NIr treatment after parkinsonian insult at both cellular and behavioural levels and suggest that Balb/c strain, due to greater penetration of NIr through skin and fur, provides a clearer model of protection than the C57BL/6 strain.

BMC Neurosci 2013 Mar 27 14(1) 40

https://www.ncbi.nlm.nih.gov/pubmed/?term=23531041

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Recommendations and practices to optimize stroke therapy: developing effective translational research programs.

Lapchak PA

FAHA, Cedars-Sinai Medical Center, Davis Research Bldg, D-2091, 110 N George Burns Rd, Los Angeles, CA 90048. paul.lapchak@cshs.org..

Stroke 2013 Mar 44(3) 841-3

https://www.ncbi.nlm.nih.gov/pubmed/?term=23391768

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Laser acupuncture for depression: A randomised double blind controlled trial using low intensity laser intervention.

Quah-Smith I, Smith C, Crawford JD, Russell J

School of Psychiatry University of New South Wales, NSW 2052, Australia. Electronic address: quahsmith@gmail.com..

INTRODUCTION: Trials of acupuncture for the treatment of depression have produced mixed results. We examined the effectiveness of laser acupuncture compared with placebo acupuncture for the treatment of major depression. METHODS: A randomised, double blinded, placebo controlled trial was conducted in Sydney, Australia. Participants aged 18-50 years with DSM-IV major depressive disorder were eligible to join the study. Forty-seven participants were randomised to receive laser acupuncture or placebo laser at acupoints LR14, CV14, LR8, HT7 and KI3. The intervention was administered twice a week for 4 weeks and once a week for another four weeks, for a total of 12 sessions. The primary outcome assessed the change in severity of depression using the Hamilton-Depression Rating Scale (HAM-D), and secondary outcomes assessed the change in severity of depression using the Quick Inventory for Depression-Self Reporting (QID-SR), the Quick Inventory for Depression-Clinician (QIDS-CL), with outcomes assessed at eight weeks. The treatment response (greater than 50% improvement in HAM-D) and remission (HAM-D<8) were analysed. RESULTS: At eight weeks participants showed greater improvement in the active laser group on the primary and clinician-rated secondary outcome measures (HAM-D (mean 9.28 (SD 6.55) vs. mean 14.14 (SD 4.78 p<0.001); QIDS-CL (mean 8.12 (SD 6.61 versus 12.68 (mean SD 3.77)) p<0.001). The self-report QIDS-SR scores improved in both groups but did not differ significantly between the groups. In the active laser group, QIDS-SR scores remained significantly lower than baseline at 3 months follow-up. Response rates (active laser, placebo laser) on ITT (intention to treat) analyses were 72.0% and 18.2% (p<0.001), respectively. Remission rates on ITT analyses (active laser, placebo laser) were 56.0% and 4.5% (p<0.001). Transient fatigue was the only adverse effect reported. LIMITATIONS: There was no follow-up for the placebo group at one and 3 months. CONCLUSION: Laser acupuncture showed a clinically and statistically significant benefit with reducing symptoms of depression on objective measures.

J Affect Disord 2013 Jan 18

https://www.ncbi.nlm.nih.gov/pubmed/?term=23337655

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Transcranial low-level laser therapy improves neurological performance in traumatic brain injury in mice: effect of treatment repetition regimen.

Xuan W, Vatansever F, Huang L, Wu Q, Xuan Y, Dai T, Ando T, Xu T, Huang YY, Hamblin MR

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Dermatology, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Otolaryngology, Traditional Chinese Medical University of Guangxi, Nanning, China..

Low-level laser (light) therapy (LLLT) has been clinically applied around the world for a spectrum of disorders requiring healing, regeneration and prevention of tissue death. One area that is attracting growing interest in this scope is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). We developed a mouse model of severe TBI induced by controlled cortical impact and explored the effect of different treatment schedules. Adult male BALB/c mice were divided into 3 broad groups (a) sham-TBI sham-treatment, (b) real-TBI sham-treatment, and (c) real-TBI active-treatment. Mice received active-treatment (transcranial LLLT by continuous wave 810 nm laser, 25 mW/cm(2), 18 J/cm(2), spot diameter 1 cm) while sham-treatment was immobilization only, delivered either as a single treatment at 4 hours post TBI, as 3 daily treatments commencing at 4 hours post TBI or as 14 daily treatments. Mice were sacrificed at 0, 4, 7, 14 and 28 days post-TBI for histology or histomorphometry, and injected with bromodeoxyuridine (BrdU) at days 21-27 to allow identification of proliferating cells. Mice with severe TBI treated with 1-laser Tx (and to a greater extent 3-laser Tx) had significant improvements in neurological severity score (NSS), and wire-grip and motion test (WGMT). However 14-laser Tx provided no benefit over TBI-sham control. Mice receiving 1- and 3-laser Tx had smaller lesion size at 28-days (although the size increased over 4 weeks in all TBI-groups) and less Fluoro-Jade staining for degenerating neurons (at 14 days) than in TBI control and 14-laser Tx groups. There were more BrdU-positive cells in the lesion in 1- and 3-laser groups suggesting LLLT may increase neurogenesis. Transcranial NIR laser may provide benefit in cases of acute TBI provided the optimum treatment regimen is employed.

PLoS One 2013 8(1) e53454

https://www.ncbi.nlm.nih.gov/pubmed/?term=23308226

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Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans.

Barrett DW, Gonzalez-Lima F

Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA..

This is the first controlled study demonstrating the beneficial effects of transcranial laser stimulation on cognitive and emotional functions in humans. Photobiomodulation with red to near-infrared light is a novel intervention shown to regulate neuronal function in cell cultures, animal models, and clinical conditions. Light that intersects with the absorption spectrum of cytochrome oxidase was applied to the forehead of healthy volunteers using the laser diode CG-5000, which maximizes tissue penetration and has been used in humans for other indications. We tested whether low-level laser stimulation produces beneficial effects on frontal cortex measures of attention, memory and mood. Reaction time in a sustained-attention psychomotor vigilance task (PVT) was significantly improved in the treated (n=20) vs. placebo control (n=20) groups, especially in high novelty-seeking subjects. Performance in a delayed match-to-sample (DMS) memory task showed also a significant improvement in treated vs. control groups as measured by memory retrieval latency and number of correct trials. The Positive and Negative Affect Schedule (PANAS-X), which tracks self-reported positive and negative affective (emotional) states over time, was administered immediately before treatment and 2weeks after treatment. The PANAS showed that while participants generally reported more positive affective states than negative, overall affect improved significantly in the treated group due to more sustained positive emotional states as compared to the placebo control group. These data imply that transcranial laser stimulation could be used as a non-invasive and efficacious approach to increase brain functions such as those related to cognitive and emotional dimensions. Transcranial infrared laser stimulation has also been proven to be safe and successful at improving neurological outcome in humans in controlled clinical trials of stroke. This innovative approach could lead to the development of non-invasive, performance-enhancing interventions in healthy humans and in those in need of neuropsychological rehabilitation.

Neuroscience 2013 Jan 29 230 13-23

https://www.ncbi.nlm.nih.gov/pubmed/?term=23200785

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Transcranial red and near infrared light transmission in a cadaveric model.

Jagdeo JR, Adams LE, Brody NI, Siegel DM

Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, New York, United States of America. jrjagdeo@gmail.com.

BACKGROUND AND OBJECTIVE: Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model. STUDY DESIGN/MATERIALS AND METHODS: To investigate this idea, we measured the transmission of near infrared light energy, using red light for purposes of comparison, through intact cadaver soft tissue, skull bones, and brain using a commercially available LED device at 830 nm and 633 nm. RESULTS: Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions. CONCLUSION: These findings indicate that near infrared light can penetrate formalin fixed soft tissue, bone and brain and implicate that benefits observed in clinical studies are potentially related to direct action of near infrared light on neural tissue.

PLoS One 2012 7(10) e47460

https://www.ncbi.nlm.nih.gov/pubmed/?term=23077622

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The brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, and induced nitric oxide synthase expressions after low-level laser therapy in an axonotmesis experimental model.

Gomes LE, Dalmarco EM, Andre ES

1 Laboratorio de Fisioterapia Neurologica Experimental (LFNE), Departamento de Fisioterapia, Universidade Regional de Blumenau (FURB) , Blumenau, Brazil ..

Abstract Background data: A robust body of evidence has shown that low-level laser therapy (LLLT) improves peripheral nerve regeneration. However, the biochemical background triggered in this process is not yet fully understood. Objective: The purpose of this study was to evaluate the mRNA expression of neurotrophic factors (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and neurotrophin-3, [NT-3]) and also an inflammatory marker (induced nitric oxide synthase [iNOS]) in an axonotmesis experimental model after low-level laser therapy. Methods: Thirty-six adult male Wistar rats (250-350 g) were subjected to right sciatic nerve crush injury, and 24 h later, the animals in the three different experimental groups (n=18) were irradiated on a daily basis with helium-neon laser (collimated HeNe laser, continuous emission, wavelength: 632.8 nm, power density: 0.5 mW/cm(2), irradiation time: 20 sec, energy density: 10 J/cm(2)) during 7, 14, and 21 consecutive days, respectively. The control group (n=18) underwent the same procedures, but with the equipment turned off. At the end of the experiments, animals were killed with an overdose of anesthesia to remove samples from the sciatic nerve lesion epicenter to determine the mRNA expression of BDNF, NGF, NT-3 and iNOS enzyme. Results: Comparisons between groups showed that HeNe laser increased the mRNA expression of both BDNF and NGF factors after 14 days of LLLT, with peak expression at the 21st day. Increase in NT-3 mRNA expression was not observed. In addition, HeNe laser produced iNOS expression reduction, which played an important role in the inflammatory process. Conclusions: The reported data could have a relevant practical value because LLLT is a noninvasive procedure, and have revealed significant increase in neurotrophic factor expressions and inflammatory process reduction, opening the possibility of using LLLT as an important aid to nerve regeneration process.

Photomed Laser Surg 2012 Nov 30(11) 642-7

https://www.ncbi.nlm.nih.gov/pubmed/?term=23003120

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Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases.

Song S, Zhou F, Chen WR

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, No, 55 Zhongshan Avenue West, Guangzhou, Tianhe District, 510631, China. zhouff@scnu.edu.cn..

ABSTRACT: BACKGROUND: Activated microglial cells are an important pathological component in brains of patients with neurodegenerative diseases. The purpose of this study was to investigate the effect of He-Ne (632.8 nm, 64.6 mW/cm2) low-level laser therapy (LLLT), a non-damaging physical therapy, on activated microglia, and the subsequent signaling events of LLLT-induced neuroprotective effects and phagocytic responses. METHODS: To model microglial activation, we treated the microglial BV2 cells with lipopolysaccharide (LPS). For the LLLT-induced neuroprotective study, neuronal cells with activated microglial cells in a Transwell cell-culture system were used. For the phagocytosis study, fluorescence-labeled microspheres were added into the treated microglial cells to confirm the role of LLLT. RESULTS: Our results showed that LLLT (20 J/cm2) could attenuate toll-like receptor (TLR)-mediated proinflammatory responses in microglia, characterized by down-regulation of proinflammatory cytokine expression and nitric oxide (NO) production. LLLT-triggered TLR signaling inhibition was achieved by activating tyrosine kinases Src and Syk, which led to MyD88 tyrosine phosphorylation, thus impairing MyD88-dependent proinflammatory signaling cascade. In addition, we found that Src activation could enhance Rac1 activity and F-actin accumulation that typify microglial phagocytic activity. We also found that Src/PI3K/Akt inhibitors prevented LLLT-stimulated Akt (Ser473 and Thr308) phosphorylation and blocked Rac1 activity and actin-based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway. CONCLUSIONS: The present study underlines the importance of Src in suppressing inflammation and enhancing microglial phagocytic function in activated microglia during LLLT stimulation. We have identified a new and important neuroprotective signaling pathway that consists of regulation of microglial phagocytosis and inflammation under LLLT treatment. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.

J Neuroinflammation 2012 9 219

https://www.ncbi.nlm.nih.gov/pubmed/?term=22989325

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Effect of low-level laser stimulation on EEG.

Wu JH, Chang WD, Hsieh CW, Jiang JA, Fang W, Shan YC, Chang YC

Department of Biomedical Engineering, Ming Chuan University, No. 5 Deming Road, Gweishan Township, Taoyuan 333, Taiwan..

Conventional laser stimulation at the acupoint can induce significant brain activation, and the activation is theoretically conveyed by the sensory afferents. Whether the insensible low-level Laser stimulation outside the acupoint could also evoke electroencephalographic (EEG) changes is not known. We designed a low-level laser array stimulator (6 pcs laser diode, wavelength 830 nm, output power 7 mW, and operation frequency 10 Hz) to deliver insensible laser stimulations to the palm. EEG activities before, during, and after the laser stimulation were collected. The amplitude powers of each EEG frequency band were analyzed. We found that the low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

Evid Based Complement Alternat Med 2012 2012 951272

https://www.ncbi.nlm.nih.gov/pubmed/?term=22973409

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A new treatment protocol using photobiomodulation and muscle/bone/joint recovery techniques having a dramatic effect on a stroke patient’s recovery: a new weapon for clinicians.

Boonswang NA, Chicchi M, Lukachek A, Curtiss D

Cardiothoracic Surgery Department, Easton Hospital, Easton, Pennsylvania, USA..

The subject of this case study is a 29-year-old woman who suffered a brainstem stroke. She remained severely dizzy, had a non-functional left hand secondary to weakness, severe spasticity in the right hand, a right lateral sixth nerve palsy and was unable to ambulate on presentation. The stroke occurred 2 years before presentation. The subject had been treated for 21 months at two different stroke rehabilitation centres before presentation. Our stroke protocol includes photobiomodulation administered with the XR3T-1 device (manufactured by THOR) and ‘muscle/bone/joint/soft tissue’ recovery techniques. The patient was seen once a week for 8 weeks and treatment sessions lasted approximately 60 mins. The results were dramatic: after 8 weeks of implementation of our protocol, the patient demonstrated positive change in every area of her deficits as determined by improvements in physical examination findings. The gains achieved at 8 weeks have been maintained to this day and she continues to be treated once every 4 weeks.

BMJ Case Rep 2012 2012

https://www.ncbi.nlm.nih.gov/pubmed/?term=22967677

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Low-Level Light Therapy Improves Cortical Metabolic Capacity and Memory Retention.

Rojas JC, Bruchey AK, Gonzalez-Lima F

Department of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, USA Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA..

Cerebral hypometabolism characterizes mild cognitive impairment and Alzheimer’s disease. Low-level light therapy (LLLT) enhances the metabolic capacity of neurons in culture through photostimulation of cytochrome oxidase, the mitochondrial enzyme that catalyzes oxygen consumption in cellular respiration. Growing evidence supports that neuronal metabolic enhancement by LLLT positively impacts neuronal function in vitro and in vivo. Based on its effects on energy metabolism, it is proposed that LLLT will also affect the cerebral cortex in vivo and modulate higher-order cognitive functions such as memory. In vivo effects of LLLT on brain and behavior are poorly characterized. We tested the hypothesis that in vivo LLLT facilitates cortical oxygenation and metabolic energy capacity and thereby improves memory retention. Specifically, we tested this hypothesis in rats using fear extinction memory, a form of memory modulated by prefrontal cortex activation. Effects of LLLT on brain metabolism were determined through measurement of prefrontal cortex oxygen concentration with fluorescent quenching oximetry and by quantitative cytochrome oxidase histochemistry. Experiment 1 verified that LLLT increased the rate of oxygen consumption in the prefrontal cortex in vivo. Experiment 2 showed that LLLT-treated rats had an enhanced extinction memory as compared to controls. Experiment 3 showed that LLLT reduced fear renewal and prevented the reemergence of extinguished conditioned fear responses. Experiment 4 showed that LLLT induced hormetic dose-response effects on the metabolic capacity of the prefrontal cortex. These data suggest that LLLT can enhance cortical metabolic capacity and retention of extinction memories, and implicate LLLT as a novel intervention to improve memory.

J Alzheimers Dis 2012 Jul 31

https://www.ncbi.nlm.nih.gov/pubmed/?term=22850314

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Irradiation of 850-nm laser light changes the neural activities in rat primary visual cortex.

Wu XY, Mou ZX, Hou WS, Zheng XL, Yao JP, Shang GB, Yin ZQ

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, China..

Although infrared laser was proven to be an alternative approach for neural stimulation, there is very little known about the neural response to infrared laser irradiation in visual cortex. This study is to investigate the effect of near-infrared laser irradiation on neural activities at the cortex level. A 850-nm pigtailed diode laser was applied to stimulate the rat primary visual cortex while the horizontal black and white stripe pattern was used as standard visual stimulation to evoke visual-evoked potential (VEP). Both amplitude and latency of VEP P100 was measured with or without infrared pulse stimulation applied in rat primary visual cortex. Paired t test and one-way analysis of variance were used to evaluate the impact of infrared irradiation and its pulse width on the amplitudes and latencies of P100, respectively. The results from our preliminary study revealed that, the pulsed near-infrared laser depressed the VEP amplitude and shortened the latency of P100; with the increment of pulse width of infrared irradiation, further decline of VEP amplitude and much shortened latency of P100 were observed. The present work suggests that near-infrared laser irradiation can alter the neural activities in primary visual cortex transiently, and could provide a novel contactless artificial neural stimulus to brain cortex with high spatial selectivity.

Lasers Med Sci 2012 Jul 20

https://www.ncbi.nlm.nih.gov/pubmed/?term=22814897

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Transcranial low level laser (light) therapy for traumatic brain injury.

Huang YY, Gupta A, Vecchio D, Arce VJ, Huang SF, Xuan W, Hamblin MR

Wellman Center for Photomedicine, Massachusetts General Hospital, BAR414, 40 Blossom Street, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Aesthetic and Plastic Center of Guangxi Medical University, Nanning, China..

We review the use of transcranial low-level laser (light) therapy (LLLT) as a possible treatment for traumatic-brain injury (TBI). The basic mechanisms of LLLT at the cellular and molecular level and its effects on the brain are outlined. Many interacting processes may contribute to the beneficial effects in TBI including neuroprotection, reduction of inflammation and stimulation of neurogenesis. Animal studies and clinical trials of transcranial-LLLT for ischemic stroke are summarized. Several laboratories have shown that LLLT is effective in increasing neurological performance and memory and learning in mouse models of TBI. There have been case report papers that show beneficial effects of transcranial-LLLT in a total of three patients with chronic TBI. Our laboratory has conducted three studies on LLLT and TBI in mice. One looked at pulsed-vs-continuous wave laser-irradiation and found 10 Hz to be superior. The second looked at four different laser-wavelengths (660, 730, 810, and 980 nm); only 660 and 810 nm were effective. The last looked at different treatment repetition regimens (1, 3 and 14-daily laser-treatments). ((c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

J Biophotonics 2012 Jul 17

https://www.ncbi.nlm.nih.gov/pubmed/?term=22807422

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[Near-infrared laser treatment of acute stroke : From bench to bedside].

Schellinger PD, Kohrmann M

Neurologische Klinik und Neurogeriatrie, Johannes Wesling Klinikum, Hans-Nolte-Str. 1, 32429, Minden, Deutschland, peter.schellinger@muehlenkreiskliniken.de..

Near-infrared laser therapy (NIRLT) as a transcranial laser therapy (TLT) is currently being investigated as a neuroreparatory and neuroprotective treatment for acute ischemic stroke patients in a pivotal phase III trial (NEST-3). In this review we cover the theoretical background, experimental studies, translational research and the clinical trial program.

Nervenarzt 2012 Aug 83(8) 966-74

https://www.ncbi.nlm.nih.gov/pubmed/?term=22801662

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Near-Infrared Photobiomodulation in an Animal Model of Traumatic Brain Injury: Improvements at the Behavioral and Biochemical Levels.

Quirk BJ, Torbey M, Buchmann E, Verma S, Whelan HT

1 Medical College of Wisconsin , Milwaukee, Wisconsin..

Abstract Objective: The purpose of this was to evaluate the neuroprotective effects of near-infrared (NIR) light using an in-vivo rodent model of traumatic brain injury (TBI), controlled cortical impact (CCI), and to characterize changes at the behavioral and biochemical levels. Background data: NIR upregulates mitochondrial function, and decreases oxidative stress. Mitochondrial oxidative stress and apoptosis are important in TBI. NIR enhanced cell viability and mitochondrial function in previous in-vitro TBI models, supporting potential NIR in-vivo benefits. Methods: Sprague-Dawley rats were divided into three groups: severe TBI, sham surgery, and anesthetization only (behavioral response only). Cohorts in each group were administered either no NIR or NIR. They received two 670 nm LED treatments (5 min, 50 mW/cm(2), 15 J/cm(2)) per day for 72 h (chemical analysis) or 10 days (behavioral). During the recovery period, animals were tested for locomotor and behavioral activities using a TruScan device. Frozen brain tissue was obtained at 72 h and evaluated for apoptotic markers and reduced glutathione (GSH) levels. Results: Significant differences were seen in the TBI plus and minus NIR (TBI+/-) and sham plus and minus NIR (S+/-) comparisons for some of the TruScan nose poke parameters. A statistically significant decrease was found in the Bax pro-apoptotic marker attributable to NIR exposure, along with lesser increases in Bcl-2 anti-apoptotic marker and GSH levels. Conclusions: These results show statistically significant, preclinical outcomes that support the use of NIR treatment after TBI in effecting changes at the behavioral, cellular, and chemical levels.

Photomed Laser Surg 2012 Jul 13

https://www.ncbi.nlm.nih.gov/pubmed/?term=22793787

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Deciphering the Neuronal Circuitry Controlling Local Blood Flow in the Cerebral Cortex with Optogenetics in PV::Cre Transgenic Mice.

Urban A, Rancillac A, Martinez L, Rossier J

Laboratoire de Neurobiologie, Equipe Optogenetics and Brain Imaging, CNRS UMR 7637, Ecole Superieure de Physique et de Chimie Industrielles ParisTech PARIS, France..

Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF.

Front Pharmacol 2012 3 105

https://www.ncbi.nlm.nih.gov/pubmed/?term=22715327

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Survival of Dopaminergic Amacrine Cells after Near-Infrared Light Treatment in MPTP-Treated Mice.

Peoples C, Shaw VE, Stone J, Jeffery G, Baker GE, Mitrofanis J

Discipline of Anatomy & Histology F13, The University of Sydney, Sydney, NSW 2006, Australia..

We examined whether near-infrared light (NIr) treatment (photobiomodulation) saves dopaminergic amacrine cells of the retina in an acute and a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. For the acute model, BALB/c mice had MPTP (100 mg/kg) or saline injections over 30 hours, followed by a six-day-survival period. For the chronic model, mice had MPTP (200 mg/kg) or saline injections over five weeks, followed by a three-week-survival period. NIr treatment was applied either at the same time (simultaneous series) or well after (posttreatment series) the MPTP insult. There were four groups within each series: Saline, Saline-NIr, MPTP, and MPTP-NIr. Retinae were processed for tyrosine hydroxylase (TH) immunochemistry, and cell number was analysed. In the MPTP groups, there was a significant reduction in TH(+) cell number compared to the saline controls; this reduction was greater in the acute (~50%) compared to the chronic (~30%) cases. In the MPTP-NIr groups, there were significantly more TH(+) cells than in the MPTP groups of both series (~30%). In summary, we showed that NIr treatment was able to both protect (simultaneous series) and rescue (posttreatment series) TH(+) cells of the retina from parkinsonian insult.

ISRN Neurol 2012 2012 850150

https://www.ncbi.nlm.nih.gov/pubmed/?term=22701184

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Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice.

Shaw VE, Peoples C, Spana S, Ashkan K, Benabid AL, Stone J, Baker GE, Mitrofanis J

Discipline of Anatomy and Histology, The University of Sydney, Sydney, NSW 2006, Australia..

We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN) and zona incerta (ZI); both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100-250 mg/kg) or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model) or over five weeks followed by a three-week survival period (chronic model). NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30-45%) the increase in Fos(+) cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number). In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.

Parkinsons Dis 2012 2012 296875

https://www.ncbi.nlm.nih.gov/pubmed/?term=22666627

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Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial.

Giannasi LC Dr, Matsui MT Dr, Batista SR Prof, Hardt CT Prof, Gomes CP Prof, Amorim JB Dr, Aguiar IC Prof, Collange L Prof, Oliveira EF Prof, Santos IR Prof, Dias IS Prof, Nassif SR Prof, Oliveira CS Dr, Oliveira LV Dr, Gomes MF Dr

ABSTRACT: BACKGROUND: Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP), given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, = 780nm) and LED ( = 660 nm) irradiation in CP patients. Methods/Design: 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing / underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. Discussion: This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies.

BMC Musculoskelet Disord 2012 May 15 13(1) 71

https://www.ncbi.nlm.nih.gov/pubmed/?term=22587485

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Nitrergic response to Clostridium perfringens infection in the rat brain regions: effect of red light irradiation.

Movsesyan HA, Alchujyan NKh, Movsesyan NH, Guevorkian AG, Hairapetyan HL, Barsegyan KA, Kevorkian GA

H.Buniatian Institute of Biochemistry NAS RA, 5/1 P. Sevak St., 0014, Yerevan, Republic of Armenia..

A single intraperitoneal injection of a gram-positive pathogen Clostridium perfringens (Cp) causes a remarkable down-regulation the constitutive nitric oxide synthase (cNOS) with a simultaneous increase in the activity of inducible NOS (iNOS) and the level of reactive nitrogen species in the rat brain major regions (cortex, striatum, hippocampus and hypothalamus) at 48 h post-administration of Cp. Treatment by both a semiconductor laser (SCL) and/or a light-emitting diode (LED) with same wavelength, energy density and time exposure (continuous wave, lambda=654 nm, fluence=1.27 J/cm(2), time exposure=600 s) could modulate brain nitrergic response following Cp-infection. Besides, unlike the LED, the SCL-irradiation prevents the cNOS inhibition in all the studied brain regions and might be useful in restoring its function in neurotransmission and cerebral blood flow, along with providing a protective effect against nitrosative stress-induced iNOS-mediated injury in the brain regions.

Cent Nerv Syst Agents Med Chem 2012 Jun 12(2) 146-52

https://www.ncbi.nlm.nih.gov/pubmed/?term=22533509

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Effect of 710-nm Visible Light Irradiation on Neuroprotection and Immune Function after Stroke.

Choi DH, Lim JH, Lee KH, Kim MY, Kim HY, Shin CY, Han SH, Lee J

Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University School of Medicine, Seoul, Republic of Korea..

Objective: The phototherapeutic effects of low level infrared laser irradiation (808 nm) on brain neuronal cell protection after stroke have been presented recently. We previously reported that 710-nm wavelength visible light (VIS) increases total lymphocyte counts in vivo, especially CD4(+) T lymphocytes. In this study, we investigated the effects of 710-nm VIS irradiation on neuronal protection and recovery correlating with cellular immunity in stroke rats. Methods: Rats were subjected to 90-min middle cerebral artery occlusion (MCAO) followed by reperfusion and were divided into two groups: irradiation and no irradiation. The irradiation group had been exposed to 710-nm VIS for 3 weeks after MCAO establishment or sham operation. The helper T cell (CD4(+)) count in the whole blood and infarct volume were measured. Messenger RNA expression levels of IL-4 and IL-10 in peripheral blood mononuclear cells were measured, a histologic study including microglia activation and regulatory T (Treg) cell markers, neurological severity scoring and a parallel bar walking test were all performed. Results: CD4(+) cell count was reduced after MCAO but was significantly increased by 710-nm VIS irradiation. The infarct sizes were decreased in the MCAO + irradiation group compared with the MCAO control group. IL-10 mRNA expression and the immunoreactivity of Treg cells were increased in the MCAO + irradiation group compared with the MCAO control group. Increased microglia activation after MCAO was reduced by 710-nm VIS irradiation. The irradiation group also showed improved neurological severity score levels and step fault scores after MCAO. Conclusions: Our data suggest that 710-nm VIS irradiation may activate cellular immunity, reduce brain infarction and ultimately induce functional recovery in a stroke animal model.

Neuroimmunomodulation 2012 Mar 30 19(5) 267-276

https://www.ncbi.nlm.nih.gov/pubmed/?term=22472725

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Transcranial laser therapy for acute ischemic stroke: a pooled analysis of NEST-1 and NEST-2.

Huisa BN, Stemer AB, Walker MG, Rapp K, Meyer BC, Zivin JA

Department of Neurology, University of New Mexico, Albuquerque, NM, USA..

BACKGROUND: NeuroThera Effectiveness and Safety Trials (NEST) 1 and 2 have demonstrated safety of transcranial laser therapy (TLT) for human treatment in acute ischemic stroke. NEST 1 study suggested efficacy of TLT but the following NEST 2, despite strong signals, missed reaching significance on its primary efficacy endpoint. In order to assess efficacy in a larger cohort, a pooled analysis was therefore performed. METHODS: The two studies were first compared for heterogeneity, and then a pooled analysis was performed to assess overall safety and efficacy, and examined particular subgroups. The primary endpoint for the pooled analysis was dichotomized modified Rankin scale (mRS) 0-2 at 90 days. RESULTS: Efficacy analysis for the intention-to-treat population was based on a total of 778 patients. Baseline characteristics and prognostic factors were balanced between the two groups. The TLT group (n = 410) success rate measured by the dichotomized 90-day mRS was significantly higher compared with the sham group (n = 368) (P = 0.003, OR: 1.67, 95% CI: 1.19-2.35). The distribution of scores on the 90-day mRS was significantly different in TLT compared with sham (P = 0.0005 Cochran-Mantel-Haenszel). Subgroup analysis identified moderate strokes as a predictor of better treatment response. CONCLUSIONS: This pooled analysis support the likelihood that transcranial laser therapy is effective for the treatment of acute ischemic stroke when initiated within 24 h of stroke onset. If ultimately confirmed, transcranial laser therapy will change management and improve outcomes of far more patients with acute ischemic stroke.

Int J Stroke 2012 Feb 2

https://www.ncbi.nlm.nih.gov/pubmed/?term=22299818

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Photobiomodulation enhances nigral dopaminergic cell survival in a chronic MPTP mouse model of Parkinson’s disease.

Peoples C, Spana S, Ashkan K, Benabid AL, Stone J, Baker GE, Mitrofanis J

Discipline of Anatomy & Histology F13, University of Sydney, Australia..

We have shown previously that photobiomodulation or near-infrared light (NIr) treatment protects dopaminergic cells of the substantia nigra pars compacta (SNc) in an acute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson’s disease (PD). In this study, we tested the protective and rescue action of NIr treatment in a chronic MPTP model, developed to resemble more closely the slow progressive degeneration in PD patients. We examined three regions of dopaminergic cells, the SNc, periaqueductal grey matter (PaG) and zona incerta-hypothalamus (ZI-Hyp). BALB/c mice had MPTP or saline injections over five weeks, followed by a three-week survival. NIr treatment was applied either at the same time as (simultaneous series) or after (post-treatment series) the MPTP insult. There were four groups within each series; Saline, Saline-NIr, MPTP and MPTP-NIr. Brains were processed for tyrosine hydroxylase (TH) immunochemistry and cell number was analysed using the optical fractionator method. In the SNc, there was a significant reduction ( approximately 45%) in TH(+) cell number in the MPTP groups compared to the saline controls of both series. In the MPTP-NIr groups of both series, TH(+) cell number was significantly higher ( approximately 25%) than in the MPTP groups, but lower than in the saline controls ( approximately 20%). By contrast in the PaG and ZI-Hyp, there were no significant differences in TH(+) cell number between the MPTP an MPTP-NIr groups of either series. In summary, exposure to NIr either at the same time or well after chronic MPTP insult saved many SNc dopaminergic cells from degeneration.

Parkinsonism Relat Disord 2012 Jan 27

https://www.ncbi.nlm.nih.gov/pubmed/?term=22285756

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Low-level laser therapy for closed-head traumatic brain injury in mice: effect of different wavelengths.

Wu Q, Xuan W, Ando T, Xu T, Huang L, Huang YY, Dai T, Dhital S, Sharma SK, Whalen MJ, Hamblin MR

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Dermatology, Harvard Medical School, Boston, Massachusetts; Department of Burns and Plastic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, China..

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) affects millions worldwide and is without effective treatment. One area that is attracting growing interest is the use of transcranial low-level laser therapy (LLLT) to treat TBI. The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may treat TBI by increasing respiration in the mitochondria, causing activation of transcription factors, reducing inflammatory mediators and oxidative stress, and inhibiting apoptosis. STUDY DESIGN/MATERIALS AND METHODS: We tested LLLT in a mouse model of closed-head TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with continuous-wave 665, 730, 810, or 980 nm lasers (36 J/cm(2) delivered at 150 mW/cm(2) ) 4-hour post-TBI and were followed up by neurological performance testing for 4 weeks. RESULTS: Mice with moderate-to-severe TBI treated with 665 and 810 nm laser (but not with 730 or 980 nm) had a significant improvement in Neurological Severity Score that increased over the course of the follow-up compared to sham-treated controls. Morphometry of brain sections showed a reduction in small deficits in 665 and 810 nm laser treated mouse brains at 28 days. CONCLUSIONS: The effectiveness of 810 nm agrees with previous publications, and together with the effectiveness of 660 nm and non-effectiveness of 730 and 980 nm can be explained by the absorption spectrum of cytochrome oxidase, the candidate mitochondrial chromophore in transcranial LLLT. Lasers Surg. Med. (c) 2012 Wiley Periodicals, Inc.

Lasers Surg Med 2012 Jan 24

https://www.ncbi.nlm.nih.gov/pubmed/?term=22275301

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Therapeutic effect of near infrared (NIR) light on Parkinson’s disease models.

Quirk BJ, Desmet KD, Henry M, Buchmann E, Wong-Riley M, Eells JT, Whelan HT

Department of Neurology, Medical College of Wisconsin, 8701 W. Watertown Plank Rd, Milwaukee, WI, 53226, USA..

Parkinson’s disease (PD) is a neurodegenerative disorder that affects large numbers of people, particularly those of a more advanced age. Mitochondrial dysfunction plays a central role in PD, especially in the electron transport chain. This mitochondrial role allows the use of inhibitors of complex I and IV in PD models, and enhancers of complex IV activity, such as NIR light, to be used as possible therapy. PD models fall into two main categories; cell cultures and animal models. In cell cultures, primary neurons, mutant neuroblastoma cells, and cell cybrids have been studied in conjunction with NIR light. Primary neurons show protection or recovery of function and morphology by NIR light after toxic insult. Neuroblastoma cells, with a gene for mutant alpha-synuclein, show similar results. Cell cybrids, containing mtDNA from PD patients, show restoration of mitochondrial transport and complex I and IV assembly. Animal models include toxin-insulted mice, and alpha-synuclein transgenic mice. Functional recovery of the animals, chemical and histological evidence, and delayed disease progression show the potential of NIR light in treating Parkinson’s disease.

Front Biosci (Elite Ed) 2012 4 818-23

https://www.ncbi.nlm.nih.gov/pubmed/?term=22201916

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Effects of low level laser therapy on proliferation and neurotrophic factor gene expression of human schwann cells in vitro.

Yazdani SO, Golestaneh AF, Shafiee A, Hafizi M, Omrani HA, Soleimani M

Neuroscience Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran; Stem Cell Biology Department, Stem Cell Technology Research Center, Tehran, Iran; Functional Neurosurgery Research Center, Department of Neurosurgery, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran..

Previous studies have been proposed that proliferation and release of certain growth factors by different types of cells can be modulated by low level laser therapy. We aimed to demonstrate the effect of laser irradiation on human schwann cell proliferation and neurotrophic factor gene expression in vitro. Human schwann cells (SCs) were harvested from sural nerve that was obtained from organ donor followed by treatment with an 810nm, 50mW diode laser (two different energies: 1J/cm(2) and 4J/cm(2)) in three consecutive days. SC proliferation was measured, after first irradiation on days 1, 4 and 7 by the MTT assay. Real time PCR analysis was utilized on days 5 and 20 to evaluate the expression of key genes involved in nerve regeneration consist of NGF, BDNF and GDNF. Evaluation of cellular proliferation following one day after laser treatment revealed significant decrease in cell proliferation compared to control group. However on day 7, significant increase in proliferation was found in both the irradiated groups in comparison with the control group. No significant difference was found between the laser treated groups. Treatment of SCs with laser resulted in significant increase in NGF gene expression on day 20. Difference between two treated groups and control group was not significant for BDNF and GDNF gene expression. Our results demonstrate that low level laser therapy stimulate human schwann cell proliferation and NGF gene expression in vitro.

J Photochem Photobiol B 2011 Nov 23

https://www.ncbi.nlm.nih.gov/pubmed/?term=22178388

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Transcranial near-infrared laser therapy applied to promote clinical recovery in acute and chronic neurodegenerative diseases.

Lapchak PA

Cedars-Sinai Medical Center, Department of Neurology, 110 North George Burns Road, D-2091, Los Angeles, CA 90048, USA. paul.lapchak@cshs.org..

One of the most promising methods to treat neurodegeneration is noninvasive transcranial near-infrared laser therapy (NILT), which appears to promote acute neuroprotection by stimulating mitochondrial function, thereby increasing cellular energy production. NILT may also promote chronic neuronal function restoration via trophic factor-mediated plasticity changes or possibly neurogenesis. Clearly, NILT is a treatment that confers neuroprotection or neurorestoration using pleiotropic mechanisms. The most advanced application of NILT is for acute ischemic stroke based upon extensive preclinical and clinical studies. In laboratory settings, NILT is also being developed to treat traumatic brain injury, Alzheimer’s disease and Parkinson’s disease. There is some intriguing data in the literature that suggests that NILT may be a method to promote clinical improvement in neurodegenerative diseases where there is a common mechanistic component, mitochondrial dysfunction and energy impairment. This article will analyze and review data supporting the continued development of NILT to treat neurodegenerative diseases.

Expert Rev Med Devices 2012 Jan 9(1) 71-83

https://www.ncbi.nlm.nih.gov/pubmed/?term=22145842

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Focal Increase in Cerebral Blood Flow After Treatment with Near-Infrared Light to the Forehead in a Patient in a Persistent Vegetative State.

Nawashiro H, Wada K, Nakai K, Sato S

1 Department of Neurosurgery, National Defense Medical College , Tokorozawa, Saitama, Japan ..

Abstract Objective: This study aimed to quantify the cerebral blood flow (CBF) after bilateral, transcranial near-infrared light-emitting diode (LED) irradiation to the forehead in a patient in a persistent vegetative state following severe head injury. Background data: Positive behavioral improvement has been observed following transcranial near-infrared light therapy in humans with chronic traumatic brain injury and acute stroke. Methods: Single-photon emission computed tomography with N-isopropyl-[123I]p-iodoamphetamine (IMP-SPECT) was performed following a series of LED treatments. Results: IMP-SPECT showed unilateral, left anterior frontal lobe focal increase of 20%, compared to the pre-treatment value for regional CBF (rCBF) for this area, following 146 LED treatments over 73 days from an array of 23×850 nm LEDs, 13 mW each, held 5 mm from the skin, 30 min per session, the power density 11.4 mW/cm(2); the energy density 20.5 J/cm(2) at the skin. The patient showed some improvement in his neurological condition by moving his left arm/hand to reach the tracheostomy tube, post-LED therapy. Conclusions: Transcranial LED might increase rCBF with some improvement of neurological condition in severely head-injured patients. Further study is warranted.

Photomed Laser Surg 2011 Nov 2

https://www.ncbi.nlm.nih.gov/pubmed/?term=22047598

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Near infrared Transcranial Laser Therapy applied at Various Modes to Mice Following Traumatic Brain Injury Significantly Reduces Long-Term Neurological Deficits.

Oron U

Ramat Aviv, Tel-Aviv, Israel, 69978; oronu@post.tau.ac.il..

Near-infrared transcranial laser therapy (TLT) has been found to modulate various biological processes including traumatic brain injury (TBI). Following TBI in mice, in this study we assessed the possibility of various near-infrared TLT modes (pulsed vs. continuous) producing a beneficial effect on the long-term neurobehavioral outcome and brain lesions of these mice. TBI was induced by a weight-drop device, and neurobehavioral function was assessed from one hour and up to 56 days post-trauma using a neurological severity score (NSS). The extent of recovery is expressed as dNSS, the difference between the initial score, and that at any other, later, time point. An 808nm Ga-Al-As diode laser was employed transcranially 4, 6 or 8 hrs post-trauma to illuminate the entire cortex of the brain. Mice were divided into several groups of 6-8 mice: one control group that received a sham treatment and experimental groups that received either TLT continuous wave (CW) or pulsed wave (PW) mode transcranially. MRI was taken prior to sacrifice 56 days post-CHI. From 5 to 28 days post-TBI, the NSS of the laser-treated mice were significantly lower (p<0.05) than the non-laser-treated, control mice. The percentage of surviving mice that demonstrated full recovery 56 days post-CHI, namely NSS=0 (as in intact mice) was the highest (63%) in the group that had received TLT in the PW mode at 100 Hz. In addition, MRI analysis demonstrated significantly smaller infarct lesion volumes in laser treated mice as compared to control. Our data suggest that non-invasive TLT of mice post-TBI provides a significant long-term functional neurological benefit, and that the pulsed laser mode at 100 Hz is the preferred mode for such treatment. Key words: low-level laser therapy; mice; traumatic brain injury; pulsed laser; motor function, MRI.

J Neurotrauma 2011 Oct 31

https://www.ncbi.nlm.nih.gov/pubmed/?term=22040267

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670 nm Laser Light and EGCG Complementarily Reduce Amyloid-beta Aggregates in Human Neuroblastoma Cells: Basis for Treatment of Alzheimer’s Disease?

Sommer AP, Bieschke J, Friedrich RP, Zhu D, Wanker EE, Fecht HJ, Mereles D, Hunstein W

1 Institute of Micro and Nanomaterials, Nanobionic Laboratory, University of Ulm , Ulm, Germany ..

Abstract Objective: The aim of the present study is to present the results of in vitro experiments with possible relevance in the treatment of Alzheimer’s disease (AD). Background Data: Despite intensive research efforts, there is no treatment for AD. One root cause of AD is the extra- and intracellular deposition of amyloid-beta (Abeta) fibrils in the brain. Recently, it was shown that extracellular Abeta can enter brain cells, resulting in neurotoxicity. Methods: After internalization of Abeta(42) into human neuroblastoma (SH-EP) cells, they were irradiated with moderately intense 670-nm laser light (1000 Wm(-2)) and/or treated with epigallocatechin gallate (EGCG). Results: In irradiated cells, Abeta(42) aggregate amounts were significantly lower than in nonirradiated cells. Likewise, in EGCG-treated cells, Abeta(42) aggregate amounts were significantly lower than in non-EGCG-treated cells. Except for the cells simultaneously laden with Abeta(42) and EGCG, there was a significant increase in cell numbers in response to laser irradiation. EGCG alone had no effect on cell proliferation. Laser irradiation significantly increased ATP levels in Abeta(42)-free cells, when compared to nonirradiated cells. Laser-induced clearance of Abeta(42) aggregates occurred at the expense of cellular ATP. Conclusions: Irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces Abeta aggregates in SH-EP cells. Transcranial penetration of moderate levels of red to near-infrared (NIR) light has already been amply exploited in the treatment of patients with acute stroke; the blood-brain barrier (BBB) penetration of EGCG has been demonstrated in animals. We hope that our approach will inspire a practical therapy for AD.

Photomed Laser Surg 2011 Oct 26

https://www.ncbi.nlm.nih.gov/pubmed/?term=22029866

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Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice.

Ando T, Xuan W, Xu T, Dai T, Sharma SK, Kharkwal GB, Huang YY, Wu Q, Whalen MJ, Sato S, Obara M, Hamblin MR

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America..

BACKGROUND AND OBJECTIVE: Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI. STUDY DESIGN/MATERIALS AND METHODS: TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2) for 12-minutes giving a fluence of 36-J/cm(2). Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test. RESULTS: The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests. CONCLUSION: The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.

PLoS One 2011 6(10) e26212

https://www.ncbi.nlm.nih.gov/pubmed/?term=22028832

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Effect of laser phototherapy on wound healing following cerebral ischemia by cryogenic injury.

Moreira MS, Velasco IT, Ferreira LS, Ariga SK, Abatepaulo F, Grinberg LT, Marques MM

School of Dentistry, Universidade de Sao Paulo, Sao Paulo 05508-000, Brazil; LIM-51, School of Medicine, Universidade de Sao Paulo, Sao Paulo, Brazil; Postgraduate Program in Biodentistry, Ibirapuera University (UNIB), Sao Paulo, SP, Brazil..

Laser phototherapy emerges as an alternative or auxiliary therapy for acute ischemic stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, but its effects are still controversial. We have previously found that laser phototherapy immunomodulates the response to focal brain damage. Following direct cortical cryogenic injury the effects of laser phototherapy on inflammation and repair was assessed after cryogenic injury (CI) to the central nervous system (CNS) of rats. The laser phototherapy was carried out with a 780nm AlGaAs diode laser. The irradiation parameters were: power of 40mW, beam area of 0.04cm(2), energy density of 3J/cm(2) (3s) in two points (0.12J per point). Two irradiations were performed at 3h-intervals, in contact mode. Rats (20 non-irradiated – controls and 20 irradiated) were used. The wound healing in the CNS was followed in 6h, 1, 7 and 14days after the last irradiation. The size of the lesions, the neuron cell viability percentages and the amount of positive GFAP labeling were statistically compared by ANOVA complemented by Tukey’s test (p<0.05). The distribution of lymphocytes, leukocytes and macrophages were also analyzed. CI created focal lesions in the cortex represented by necrosis, edema, hemorrhage and inflammatory infiltrate. The most striking findings were: lased lesions showed smaller tissue loss than control lesions in 6h. During the first 24h the amount of viable neurons was significantly higher in the lased group. There was a remarkable increase in the amount of GFAP in the control group by 14days. Moreover, the lesions of irradiated animals had fewer leukocytes and lymphocytes in the first 24h than controls. Considering the experimental conditions of this study it was concluded that laser phototherapy exerts its effect in wound healing following CI by controlling the brain damage, preventing neuron death and severe astrogliosis that could indicate the possibility of a better clinical outcome.

J Photochem Photobiol B 2011 Oct 4

https://www.ncbi.nlm.nih.gov/pubmed/?term=22024356

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Potential for transcranial laser or LED therapy to treat stroke, traumatic brain injury, and neurodegenerative disease.

Naeser MA, Hamblin MR

Photomed Laser Surg 2011 Jul 29(7) 443-6

https://www.ncbi.nlm.nih.gov/pubmed/?term=21728786

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The effect of low-energy laser irradiation on apoptotic factors following experimentally induced transient cerebral ischemia.

Yip KK, Lo, SC, Leung, MC, So, KF, Tang, CY, Poon, DM

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong..

Apoptosis, or programmed cell death, resulting from cerebral ischemia may be related to decreased levels of anti-apoptotic factors, such as serine/threonine kinase (Akt), phosphorylated Akt (pAkt), pBAD, and Bcl-2, and increased levels of pro-apoptotic factors, such as BAD, caspase 9, and caspase 3 activities. In this study, we investigated the effects of low-energy laser (660 nm) irradiation (LLI) on the levels and activity of various anti- and pro-apoptotic factors following ischemia. Transient cerebral ischemia was induced in Sprague-Dawley rats by unilateral occlusion of the middle cerebral artery for 1 h, followed by reperfusion. LLI was then directed on the cerebrum for varying lengths of duration (1, 5, or 10 min at an energy density of 2.64 J/cm(2), 13.2 J/cm(2), and 24.6 J/cm(2), respectively). The expression levels of Akt, pAkt, BAD, pBAD, Bcl-2, caspase 9, and caspase 3 activities were measured 4 days after injury. The levels of Akt, pAkt, Bcl-2, and pBAD were significantly increased following laser irradiation. In addition, LLI significantly decreased caspase 9 and caspase 3 activities caused by ischemia-reperfusion. LLI may protect the brain by upregulating Akt, pAkt, pBAD, and Bcl-2 expression and downregulating caspase 9 and caspase 3 expression following transient cerebral ischemia. This modality is a promising protective therapeutic intervention after strokes or other ischemic events.

Neuroscience 2011 Jun 17

https://www.ncbi.nlm.nih.gov/pubmed/?term=21712070

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Noninvasive brain stimulation in traumatic brain injury.

Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Bernabeu M, Tormos JM, Pascual-Leone A

Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA..

OBJECTIVE: To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). METHODS: Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. MAIN FINDINGS: We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. CONCLUSIONS: Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.

J Head Trauma Rehabil 2012 Jul-Aug 27(4) 274-92

https://www.ncbi.nlm.nih.gov/pubmed/?term=21691215

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Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety.

Tanaka Y, Akiyoshi J, Kawahara Y, Ishitobi Y, Hatano K, Hoaki N, Mori A, Goto S, Tsuru J, Matsushita H, Hanada H, Kodama K, Isogawa K, Kitamura H, Fujikura Y

Department of Neuropsychiatry, Oita University Faculty of Medicine, Hasama-Machi, Yufu-Shi, Oita, Japan..

BACKGROUND: Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans. OBJECTIVE: The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model. METHODS: Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test. RESULTS: Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group. CONCLUSIONS: These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects.

Brain Stimul 2011 Apr 4(2) 71-6

https://www.ncbi.nlm.nih.gov/pubmed/?term=21511206

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Violet laser acupuncture-part 1: effects on brain circulation.

Litscher G, Huang T, Wang L, Zhang W

Research Unit of Biomedical Engineering in Anesthesia and Intensive Care Medicine and TCM Research Center Graz, Medical University of Graz, Graz, Austria..

Violet laser acupuncture using a wavelength of 405 nm has been investigated in only a few scientific studies. The aim of this study was to provide selective evidence of a specific effect of violet laser acupuncture on mean cerebral blood flow velocity using a Doppler ultrasound technique. A transcranial Doppler sonography construction was developed especially for this study to monitor blood flow profiles in the basilar and middle cerebral arteries simultaneously and continuously. The acupuncture point Dazhui on the upper back was tested in a controlled study with 10 healthy volunteers (24.9 +/- 3.3 years, mean age +/- SD; 5 females, 5 males). In addition to an on/off-effect, violet laser stimulation increased the blood flow velocity in the basilar artery significantly (p < 0.001) compared with the reference interval before laser acupuncture. In the middle cerebral artery, only minimal, nonsignificant changes in blood flow velocity were seen. Metal needle acupuncture at the same point intensified the effects; however, blood flow profiles did not change significantly during and after stimulation with a deactivated violet laser.

J Acupunct Meridian Stud 2010 Dec 3(4) 255-9

https://www.ncbi.nlm.nih.gov/pubmed/?term=21185540

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Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports.

Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA

1 VA Boston Healthcare System , Boston, Massachusetts..

Abstract Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1” diameter, 61 diodes (9 x 633 nm, 52 x 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. Conclusions: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.

Photomed Laser Surg 2010 Dec 23

https://www.ncbi.nlm.nih.gov/pubmed/?term=21182447

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Transcranial Laser Therapy Attenuates Amyloid-beta Peptide Neuropathology in Amyloid-beta Protein Precursor Transgenic Mice.

Taboada LD, Yu J, El-Amouri S, Gattoni-Celli S, Richieri S, McCarthy T, Streeter J, Kindy MS

PhotoThera, Inc., Carlsbad, CA..

Transcranial laser therapy (TLT) was tested for efficacy in a mouse model of Alzheimer’s disease (AD) using a near-infrared energy laser system. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal function. Studies were performed to determine the effect of TLT in an amyloid-beta protein precursor (AbetaPP) transgenic mouse model. TLT was administered 3 times/week at various doses, starting at 3 months of age, and was compared to a control group (no laser treatment). Treatment was continued for a total of six months. Animals were examined for amyloid load, inflammatory markers, brain amyloid-beta (Abeta) levels, plasma Abeta levels, cerebrospinal fluid Abeta levels, soluble AbetaPP (sAbetaPP) levels, and behavioral changes. The numbers of Abeta plaques were significantly reduced in the brain with administration of TLT in a dose-dependent fashion. Administration of TLT was associated with a dose-dependent reduction in amyloid load. All TLT doses mitigated the behavioral effects seen with advanced amyloid deposition and reduce the expression of inflammatory markers in the AbetaPP transgenic mice. All TLT doses produced an increase in sAbetaPPalpha and a decrease in CTFbeta levels consistent with inhibition of the beta-secretase activity. In addition, TLT showed an increase in ATP levels, mitochondrial function, and c-fos suggesting an overall improvement in neurological function. These studies suggest that TLT is a potential candidate for treatment of AD.

J Alzheimers Dis 2010 Nov 29

https://www.ncbi.nlm.nih.gov/pubmed/?term=21116053

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Taking a light approach to treating acute ischemic stroke patients: Transcranial near-infrared laser therapy translational science.

Lapchak PA

Cedars-Sinai Medical Center, Department of Neurology, Los Angeles, California, USA..

Abstract Transcranial near-infrared laser therapy (NILT) has been investigated as a novel neuroprotective treatment for acute ischemic stroke (AIS), for approximately 10 years. Two clinical trials, NeuroThera Effectiveness and Safety Trial (NEST)-1 and NEST-2, have evaluated the use of NILT to promote clinical recovery in patients with AIS. This review covers preclinical, translational, and clinical studies documented during the period 1997-2010. The primary aim of this article is to detail the development profile of NILT to treat AIS. Secondly, insight into possible mechanisms involved in light therapy will be presented. Lastly, possible new directions that should be considered to improve the efficacy profile of NILT in AIS patients will be discussed. The use of NILT was advanced to clinical trials based upon extensive translational research using multiple species. NILT, which may promote functional and behavioral recovery via a mitochondrial mechanism and by enhancing cerebral blood flow, may eventually be established as an Food and Drug Administration (FDA)-approved treatment for stroke. The NEST-3 trial, which is the pivotal trial for FDA approval, should incorporate hypotheses derived from translational studies to ensure efficacy in patients. Future NILT studies should consider administration of a thrombolytic to enhance cerebral reperfusion alongside NILT neuroprotection.

Ann Med 2010 Dec 42(8) 576-86

https://www.ncbi.nlm.nih.gov/pubmed/?term=21039081

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Long-term safety of single and multiple infrared transcranial laser treatments in Sprague-Dawley rats.

McCarthy TJ, De Taboada L, Hildebrandt PK, Ziemer EL, Richieri SP, Streeter J

PhotoThera, Inc., 5925 Priestly Drive, Suite 120, Carlsbad, California, USA. tmccarthy@photothera.com.

BACKGROUND AND OBJECTIVE: Growing interest exists in the use of near-infrared laser therapies for the treatment of numerous neurologic conditions, including acute ischemic stroke, traumatic brain injury, Parkinson’s disease, and Alzheimer’s disease. In consideration of these trends, the objective of this study was to evaluate the long-term safety of transcranial laser therapy with continuous-wave (CW) near-infrared laser light (wavelength, 808 +/- 10 nm, 2-mm diameter) with a nominal radiant power of 70 mW; power density, 2,230 mW/cm(2), and energy density, 268 J/cm(2) at the scalp (10 mW/cm(2) and 1.2 J/cm(2) at the cerebral cortical surface) in healthy Sprague-Dawley rats. MATERIALS AND METHODS: In this study, 120 anesthetized rats received sequential transcranial laser treatments to the right and left parietal areas of the head on the same day (minimum of 5 min between irradiation of each side), on either Day 1 or on each of Days 1, 3, and 5. Sixty anesthetized rats served as sham controls. Rats were evaluated 1 year after treatment for abnormalities in clinical hematology and brain and pituitary gland histopathology. RESULTS: No toxicologically important differences were found in the clinical hematology results between sham-control and laser-treated rats for any hematologic parameters examined. All values fell within historic control reference ranges for aged Sprague-Dawley rats. Similarly, brain and pituitary gland histopathology showed no treatment-related abnormalities or induced neoplasia. CONCLUSIONS: Single and multiple applications of transcranial laser therapy with 808-nm CW laser light at a nominal power density of 10 mW/cm(2) at the surface of the cerebral cortex appears to be safe in Sprague-Dawley rats 1 year after treatment.

Photomed Laser Surg 2010 Oct 28(5) 663-7

https://www.ncbi.nlm.nih.gov/pubmed/?term=20961232

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Different brain network activations induced by modulation and nonmodulation laser acupuncture.

Hsieh CW, Wu JH, Hsieh CH, Wang QF, Chen JH

Department of Photonic and Communication Engineering, Asia University, Taichung 41354, Taiwan..

The aim of this study is to compare the distinct cerebral activation with continued wave (CW) and 10 Hz-modulated wave (MW) stimulation during low-level laser acupuncture. Functional magnetic resonance imaging (fMRI) studies were performed to investigate the possible mechanism during laser acupuncture stimulation at the left foot’s yongquan (K1) acupoint. There are 12 healthy right-handed volunteers for each type of laser stimulation (10-Hz-Modulated wave: 8 males and 4 females; continued wave: 9 males and 3 females). The analysis of multisubjects in this experiment was applied by random-effect (RFX) analysis. In CW groups, significant activations were found within the inferior parietal lobule, the primary somatosensory cortex, and the precuneus of left parietal lobe. Medial and superior frontal gyrus of left frontal lobe were also aroused. In MW groups, significant activations were found within the primary motor cortex and middle temporal gyrus of left hemisphere and bilateral cuneus. Placebo stimulation did not show any activation. Most activation areas were involved in the functions of memory, attention, and self-consciousness. The results showed the cerebral hemodynamic responses of two laser acupuncture stimulation modes and implied that its mechanism was not only based upon afferent sensory information processing, but that it also had the hemodynamic property altered during external stimulation.

Evid Based Complement Alternat Med 2011 2011

https://www.ncbi.nlm.nih.gov/pubmed/?term=20953400

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Low energy laser light (632.8 nm) suppresses amyloid-beta peptide-induced oxidative and inflammatory responses in astrocytes.

Yang X, Askarova S, Sheng W, Chen JK, Sun AY, Sun GY, Yao G, Lee JC

Department of Biological Engineering, University of Missouri, Columbia, MO 65211, USA..

Oxidative stress and inflammation are important processes in the progression of Alzheimer’s disease (AD). Recent studies have implicated the role of amyloid beta-peptides (Abeta) in mediating these processes. In astrocytes, oligomeric Abeta induces the assembly of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complexes resulting in its activation to produce anionic superoxide. Abeta also promotes production of pro-inflammatory factors in astrocytes. Since low energy laser has previously been reported to attenuate oxidative stress and inflammation in biological systems, the objective of this study was to examine whether this type of laser light was able to abrogate the oxidative and inflammatory responses induced by Abeta. Primary rat astrocytes were exposed to Helium-Neon laser (lambda=632.8 nm), followed by the treatment with oligomeric Abeta. Primary rat astrocytes were used to measure Abeta-induced production of superoxide anions using fluorescence microscopy of dihydroethidium (DHE), assembly of NADPH oxidase subunits by the colocalization between the cytosolic p47(phox) subunit and the membrane gp91(phox) subunit using fluorescent confocal microscopy, phosphorylation of cytosolic phospholipase A(2) cPLA(2) and expressions of pro-inflammatory factors including interleukin-1beta (IL-1beta) and inducible nitric-oxide synthase (iNOS) using Western blot Analysis. Our data showed that laser light at 632.8 nm suppressed Abeta-induced superoxide production, colocalization between NADPH oxidase gp91(phox) and p47(phox) subunits, phosphorylation of cPLA(2,) and the expressions of IL-1beta and iNOS in primary astrocytes. We demonstrated for the first time that 632.8 nm laser was capable of suppressing cellular pathways of oxidative stress and inflammatory responses critical in the pathogenesis in AD. This study should prove to provide the groundwork for further investigations for the potential use of laser therapy as a treatment for AD.

Neuroscience 2010 Sep 25

https://www.ncbi.nlm.nih.gov/pubmed/?term=20884337

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The brain effects of laser acupuncture in healthy individuals: an FMRI investigation.

Quah-Smith I, Sachdev PS, Wen W, Chen X, Williams MA

School of Psychiatry, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia..

BACKGROUND: As laser acupuncture is being increasingly used to treat mental disorders, we sought to determine whether it has a biologically plausible effect by using functional magnetic resonance imaging (fMRI) to investigate the cerebral activation patterns from laser stimulation of relevant acupoints. METHODOLOGY/PRINCIPAL FINDINGS: Ten healthy subjects were randomly stimulated with a fibreoptic infrared laser on 4 acupoints (LR14, CV14, LR8 and HT7) used for depression following the principles of Traditional Chinese Medicine (TCM), and 1 control non-acupoint (sham point) in a blocked design (alternating verum laser and placebo laser/rest blocks), while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from the whole brain on a 3T scanner. Many of the acupoint laser stimulation conditions resulted in different patterns of neural activity. Regions with significantly increased activation included the limbic cortex (cingulate) and the frontal lobe (middle and superior frontal gyrus). Laser acupuncture tended to be associated with ipsilateral brain activation and contralateral deactivation that therefore cannot be simply attributed to somatosensory stimulation. CONCLUSIONS/SIGNIFICANCE: We found that laser stimulation of acupoints lead to activation of frontal-limbic-striatal brain regions, with the pattern of neural activity somewhat different for each acupuncture point. This is the first study to investigate laser acupuncture on a group of acupoints useful in the management of depression. Differing activity patterns depending on the acupoint site were demonstrated, suggesting that neurological effects vary with the site of stimulation. The mechanisms of activation and deactivation and their effects on depression warrant further investigation.

PLoS One 2010 5(9)

https://www.ncbi.nlm.nih.gov/pubmed/?term=20838644

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Targeted increase in cerebral blood flow by transcranial near-infrared laser irradiation.

Uozumi Y, Nawashiro H, Sato S, Kawauchi S, Shima K, Kikuchi M

Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan..

BACKGROUND AND OBJECTIVE: Brain function is highly dependent on cerebral blood flow (CBF). The precise mechanisms by which blood flow is controlled by NIR laser irradiation on the central nervous system (CNS) have not been elucidated. In this study, we examined the effect of 808 nm laser diode irradiation on CBF in mice. STUDY DESIGN/MATERIALS AND METHODS: We examined the effect of NIR irradiation on CBF at three different power densities (0.8, 1.6 and 3.2 W/cm(2)) and directly measured nitric oxide (NO) in brain tissue during NIR laser irradiation using an amperometric NO-selective electrode. We also examined the contribution of NO and a neurotransmitter, glutamate, to the regulation of CBF by using a nitric oxide synthase (NOS) inhibitor, N(g)-nitro-L-arginine methyl ester hydrochloride (L-NAME), and an N-methyl-D-aspartate (NMDA) receptor blocker, MK-801, respectively. We examined the change in brain tissue temperature during NIR laser irradiation. We also investigated the protection effect of NIR laser irradiation on transient cerebral ischemia using transient bilateral common carotid artery occlusion (BCCAO) in mice. RESULTS: We showed that NIR laser irradiation (1.6 W/cm(2) for 15-45 minutes) increased local CBF by 30% compared to that in control mice. NIR laser irradiation also induced a significant increase in cerebral NO concentration. In mice that received L-NAME, NIR laser irradiation did not induce any increase in CBF. Mice administered MK-801 showed an immediate increase but did not show a delayed additional increase in local CBF. The increase in brain tissue temperature induced by laser irradiation was estimated to be as low as 0.8 degrees C at 1.6 W/cm(2), indicating that the heating effect is not a main mechanism of the CBF increase in this condition. Pretreatment with NIR laser irradiation improved residual CBF and reduced the numbers of apoptotic cells in the hippocampus. CONCLUSION: Our data suggest that NIR laser irradiation is a promising experimental and therapeutic tool in the field of cerebral circulation research.

Lasers Surg Med 2010 Aug 42(6) 566-76

https://www.ncbi.nlm.nih.gov/pubmed/?term=20662034

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The evolution of transcranial laser therapy for acute ischemic stroke, including a pooled analysis of NEST-1 and NEST-2.

Stemer AB, Huisa BN, Zivin JA

University of California, San Diego Medical Center, Medical Office North, 3rd floor, Suite 3, 200 West Arbor Drive #8466, San Diego, CA 92103-8466, USA..

Intravenous tissue plasminogen activator is the only proven therapy for acute ischemic stroke. Not enough patients are eligible for treatment and additional new therapies are needed. Recently, laser technology has been applied to acute ischemic stroke. This noninvasive technique uses near-infrared wavelengths applied to the scalp within 24 h of symptom onset. The mechanism is incompletely understood but may involve increased mitochondrial adenosine triphosphate production. Animal models demonstrated safety and efficacy warranting randomized controlled trials in humans. NEST-1 (phase 2) and NEST-2 (phase 3) confirmed the safety of transcranial laser therapy, although efficacy was not found in NEST-2. Pooled analysis of NEST-1 and NEST-2 revealed a significantly improved success rate in patients treated with laser therapy. Further phase 3 testing is planned and may create a new paradigm for the treatment of acute ischemic stroke.

Curr Cardiol Rep 2010 Jan 12(1) 29-33

https://www.ncbi.nlm.nih.gov/pubmed/?term=20425181

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Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety.

Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR

The Department of Psychiatry, Harvard Medical School and the Developmental Biopsychiatry Research Program, McLean Hospital, 115 Mill Street Belmont, MA 02478 USA. fschiffer@mclean.harvard.edu..

ABSTRACT: BACKGROUND: Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient’s left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects. METHODS: We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain. RESULTS: At 2-weeks post treatment 6 of 10 patients had a remission (a score
Behav Brain Funct 2009 5 46

https://www.ncbi.nlm.nih.gov/pubmed/?term=19995444

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Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5′-triphosphate (ATP) content following embolic strokes in rabbits.

Lapchak PA, De Taboada L

University of California San Diego, Department of Neuroscience, 9500 Gilman Drive MTF316, La Jolla, CA 92093-0624, USA..

Transcranial near infrared laser therapy (NILT) improves behavioral outcome following embolic strokes in embolized rabbits and clinical rating scores in acute ischemic stroke (AIS) patients; however, the cellular mechanism(s) involved in NILT neuroprotection have not been elucidated. It has been proposed that mitochondrial energy production may underlie a response to NILT, but this has not been demonstrated using an in vivo embolic stroke model. Thus, we evaluated the effect of NILT on cortical ATP content using the rabbit small clot embolic stroke model (RSCEM), the model originally used to demonstrate NILT efficacy and initiate the NEST-1 clinical trial. Five minutes following embolization, rabbits were exposed to 2 min of NILT using an 808 nm laser source, which was driven to output either continuous wave (CW), or pulsed wave modes (PW). Three hours after embolization, the cerebral cortex was excised and processed for the measurement of ATP content using a standard luciferin-luciferase assay. NILT-treated rabbits were directly compared to sham-treated embolized rabbits and naive control rabbits. Embolization decreased cortical ATP content in ischemic cortex by 45% compared to naive rabbits, a decrease that was attenuated by CW NILT which resulted in a 41% increase in cortical ATP content compared to the sham embolized group (p>0.05). The absolute increase in ATP content was 22.5% compared to naive rabbits. Following PW NILT, which delivered 5 (PW1) and 35 (PW2) times more energy than CW, we measured a 157% (PW1 p=0.0032) and 221% (PW2 p=0.0001) increase in cortical ATP content, respectively, compared to the sham embolized group. That represented a 41% and 77% increase in ATP content compared to naive control rabbits. This is the first demonstration that embolization can decrease ATP content in rabbit cortex and that NILT significantly increases cortical ATP content in embolized rabbits, an effect that is correlated with cortical fluence and the mode of NILT delivery. The data provide new insight into the molecular mechanisms associated with clinical improvement following NILT.

Brain Res 2009 Oct 23

https://www.ncbi.nlm.nih.gov/pubmed/?term=19837048

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Reduced axonal transport in Parkinson’s disease cybrid neurites is restored by light therapy.

Trimmer PA, Schwartz KM, Borland MK, De Taboada L, Streeter J, Oron U

University of Virginia, Morris K Udall Parkinson’s Research Center of Excellence and Department of Neurology, Charlottesville, Virginia, USA. pat5q@virginia.edu..

ABSTRACT: BACKGROUND: It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson’s disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid “cytoplasmic hybrid” neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT). The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC) enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT). Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm2) for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined. RESULTS: The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM) was significantly reduced (p < 0.02) compared to mitochondrial movement in disease free CNT cybrid neuronal cells (0.232 +/- 0.017 SEM). For two hours after LLLT, the average velocity of mitochondrial movement in PD cybrid neurites was significantly (p < 0.003) increased (to 0.224 +/- 0.02 SEM) and restored to levels comparable to CNT. Mitochondrial movement in CNT cybrid neurites was unaltered by LLLT (0.232 +/- 0.017 SEM). Assembly of complexes in the mtETC was reduced and oxygen utilization was altered in PD cybrid neuronal cells. PD cybrid neuronal cell lines with the most dysfunctional mtETC assembly and oxygen utilization profiles were least responsive to LLLT. CONCLUSION: The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.

Mol Neurodegener 2009 4 26

https://www.ncbi.nlm.nih.gov/pubmed/?term=19534794

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[Effect of infrared low-intensity laser radiation on a mutation process and proliferative corneal activity in experimental cerebral hypoxia].

Shurygina IP, Galenkina NM, Shkurat TP

The paper deals with the impact of infrared low-intensity laser radiation (IRLILR) on a mutation process and the proliferative activity of the animal cornea during stimulation of circulatory brain hypoxia. During an experiment on laboratory albino rats, IRLILR was studied for its impact on the level of chromosomal rearrangements and the mitotic index in the corneal cells was calculated in circulatory brain hypoxia. Laser exposure during stimulation of circulatory brain hypoxia favors normalization of the level of chromosomal aberrations and a mitotic cycle in the rat corneal epithelial cells. The experimental findings suggest that IRLILR may be used in ophthalmological care for antihypoxic purposes.

Vestn Oftalmol 2009 Mar-Apr 125(2) 24-6

https://www.ncbi.nlm.nih.gov/pubmed/?term=19517827

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Effects of low-power laser irradiation on the threshold of electrically induced paroxysmal discharge in rabbit hippocampus CA1.

Kogure S, Takahashi S, Saito N, Kozuka K, Matsuda Y

Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo, 192-8577, Japan, kogure@t.soka.ac.jp..

In acute experiments using adult rabbits, we measured the paroxysmal discharge threshold (PADT) elicited by stimulation to the apical dendritic layer of the hippocampal CA1 region before and after low-power laser irradiation. Nd:YVO(4) laser irradiation (wavelength: 532 nm) was introduced into the same region as the stimulation site. The average PADT was 247 +/- 13 muA (n = 18) before laser irradiation, while after 5-min laser irradiation with 50, 75, and 100 mW, PADT was 333 +/- 40 (n = 4), 353 +/- 33 (n = 4) and 367 +/- 27 muA (n = 6), respectively. The latter two increments were statistically significant compared to the control (p < 0.05 and p < 0.01). After 10-min laser irradiation with 75 and 100 mW, PADT was 340 +/- 47 (n = 9) and 480 +/- 60 muA (n = 11; p < 0.01), respectively. Laser irradiation with a specific wavelength and average power offers the potential to suppress the generation of paroxysmal discharges in rabbit hippocampus CA1. Correlation analyses suggest that PADT increments are based on photochemical as well as photothermal effects of laser irradiation.

Lasers Med Sci 2009 May 22

https://www.ncbi.nlm.nih.gov/pubmed/?term=19462168

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The cybrid model of sporadic Parkinson’s disease.

Trimmer PA, Bennett JP Jr

Morris K. Udall Parkinson’s Disease Research Center of Excellence, Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA..

Parkinson’s disease (PD) is the eponym attached to the most prevalent neurodegenerative movement disorder of adults, derived from observations of an early nineteenth century physician and paleontologist, James Parkinson, and is now recognized to encompass much more than a movement disorder clinically or dopamine neuron death pathologically. Most PD ( approximately 90%) is sporadic (sPD), is associated with mitochondrial deficiencies and has been studied in cell and animal models arising from the use of mitochondrial toxins that unfortunately have not predicted clinical efficacy to slow disease progression in humans. We have extensively studied the cytoplasmic hybrid (“cybrid”) model of sPD in which donor mtDNAs are introduced into and expressed in neural tumor cells with identical nuclear genetic and environmental backgrounds. sPD cybrids demonstrate many abnormalities in which increased oxidative stress drives downstream antioxidant response and cell death activating signaling pathways. sPD cybrids regulate mitochondrial ETC genes and gene ontology families like sPD brain. sPD cybrids spontaneously form Lewy bodies and Lewy neurites, linking mtDNA expression to neuropathology, and demonstrate impaired organelle transport in processes and reduced mitochondrial respiration. Our recent studies show that near-infrared laser light therapy normalizes mitochondrial movement and can stimulate respiration in sPD cybrid neurons, and mitochondrial gene therapy can restore respiration and stimulate mitochondrial ETC gene and protein expression. sPD cybrids have provided multiple lines of circumstantial evidence linking mtDNA to sPD pathogenesis and can serve as platforms for therapy development. sPD cybrid models can be improved by the use of non-tumor human stem cell-derived neural precursor cells and by an introduction of postmortem brain mtDNA to test its causality directly.

Exp Neurol 2009 Mar 26

https://www.ncbi.nlm.nih.gov/pubmed/?term=19328199

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Laser therapy of painful shoulder and shoulder-hand syndrome in treatment of patients after the stroke.

Karabegovic A, Kapidzic-Durakovic S, Ljuca F

Clinic for Physical Medicine and Rehabilitation, University Clinical Centre, Faculty of Medicine, University of Tuzla, Trnovac b.b., 75 000 Tuzla, Bosnia and Herzegovina..

The common complication after stroke is pain and dysfunction of shoulder of paralyzed arm, as well as the swelling of the hand. The aim of this study was to determine the effects of LASER therapy and to correlate with electrotherapy (TENS, stabile galvanization) in subjects after stroke. We analyzed 70 subjects after stroke with pain in shoulder and oedema of paralyzed hand. The examinees were divided in two groups of 35, and they were treated in the Clinic for Physical Medicine and Rehabilitation in Tuzla during 2006 and 2007. Experimental group (EG) had a treatment with LASER, while the control group (CG) was treated with electrotherapy. Both groups had kinesis therapy and ice massage. All patients were examined on the admission and discharge by using the VAS, DASH, Barthel index and FIM. The pain intensity in shoulder was significantly reduced in EG (p<0,0001), swelling is lowered in EG (p=0,01). Barthel index in both groups was significant higher (p<0,01). DASH was significantly improved after LASER therapy in EG (p<0,01). EG had higher level of independency (p<0,01). LASER therapy used on EG shows significantly better results in reducing pain, swelling, disability and improvement of independency.

Bosn J Basic Med Sci 2009 Feb 9(1) 59-65

https://www.ncbi.nlm.nih.gov/pubmed/?term=19284397

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Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke.

Zivin JA, Albers GW, Bornstein N, Chippendale T, Dahlof B, Devlin T, Fisher M, Hacke W, Holt W, Ilic S, Kasner S, Lew R, Nash M, Perez J, Rymer M, Schellinger P, Schneider D, Schwab S, Veltkamp R, Walker M, Streeter J

From the Department of Neurosciences, University of California San Diego, La Jolla, Calif; Stanford Stroke Center, Stanford University Medical Center, Palo Alto, Calif; Tel Aviv Medical Center, Tel Aviv, Israel; Scripps Hospital, Encinitas, Calif; Sahlgrenska University Hospital, Gothenburg, Sweden; Erlanger Health System, Chattanooga, Tenn; University of Massachusetts Medical School, Worcester, Mass; Department of Neurology, Universitat Heidelberg, Heidelberg, Germany; Fawcett Memorial Hospital, Port Charlotte, Fla; Triage Wireless, Inc, San Diego, Calif; the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pa; Boston University, Boston, Mass; DeKalb Neurology Associates, Decatur, Ga; Hospital Nacional Dos de Mayo, Lima, Peru; St. Luke’s Health System, Kansas City, Mo; Universitatsklinikum Erlangen, Erlangen, Germany; the Department of Neurology, Universitat Leipzig, Leipzig, Germany; Universitatsklinikum Erlangen, Erlangen, Germany; Department of Neurology, Universitat Heidelberg, Heidelberg, Germany; Stanford Center for Biomedical Informatics Research, Stanford School of Medicine, Palo Alto, Calif; and PhotoThera, Inc, Carlsbad, Calif..

BACKGROUND AND PURPOSE: We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial-2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke. METHODS: This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score. RESULTS: We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P=0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of <16 showed a favorable outcome at 90 days on the primary end point (P<0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively. CONCLUSIONS: TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned.

Stroke 2009 Feb 20

https://www.ncbi.nlm.nih.gov/pubmed/?term=19233936

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Effect of three different intensities of infrared laser energy on the levels of amino acid neurotransmitters in the cortex and hippocampus of rat brain.

Ahmed NA, Radwan NM, Ibrahim KM, Khedr ME, El Aziz MA, Khadrawy YA

Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt..

OBJECTIVE: The aim of this study is to investigate the effects of three different intensities of infrared diode laser radiation on amino acid neurotransmitters in the cortex and hippocampus of rat brain. BACKGROUND DATA: Lasers are known to induce different neurological effects such as pain relief, anesthesia, and neurosuppressive effects; however, the precise mechanisms of these effects are not clearly elucidated. Amino acid neurotransmitters (glutamate, aspartate, glutamine, gamma-aminobutyric acid [GABA], glycine, and taurine) play vital roles in the central nervous system (CNS). MATERIALS AND METHODS: The shaved scalp of each rat was exposed to different intensities of infrared laser energy (500, 190, and 90 mW) and then the rats were sacrificed after 1 h, 7 d, and 14 d of daily laser irradiation. The control groups were exposed to the same conditions but without exposure to laser. The concentrations of amino acid neurotransmitters were measured by high-performance liquid chromatography (HPLC). RESULTS: The rats subjected to 500 mW of laser irradiation had a significant decrease in glutamate, aspartate, and taurine in the cortex, and a significant decrease in hippocampal GABA. In the cortices of rats exposed to 190 mW of laser irradiation, an increase in aspartate accompanied by a decrease in glutamine were observed. In the hippocampus, other changes were seen. The rats irradiated with 90 mW showed a decrease in cortical glutamate, aspartate, and glutamine, and an increase in glycine, while in the hippocampus an increase in glutamate, aspartate, and GABA were recorded. CONCLUSION: We conclude that daily laser irradiation at 90 mW produced the most pronounced inhibitory effect in the cortex after 7 d. This finding may explain the reported neurosuppressive effect of infrared laser energy on axonal conduction of hippocampal and cortical tissues of rat brain.

Photomed Laser Surg 2008 Oct 26(5) 479-88

https://www.ncbi.nlm.nih.gov/pubmed/?term=18800949

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Laser therapy in acute stroke treatment.

Yip S, Zivin J

Department of Neuroscience, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA..

Recent development of near infrared light therapy (NILT) as an acute stroke treatment is promising. In various preclinical animal stroke models, NILT has been shown to be effective in improving long-term stroke outcome. More importantly, NILT has a long postischemic therapeutic window that has not been previously observed in other treatment modalities. The preliminary efficacy and safety of NILT in acute stroke patients were demonstrated in the recently published phase II NeuroThera Effectiveness and Safety Trial (NEST-1). If confirmed by the NEST-II trial, NILT will revolutionize acute stroke management as ut has a long time window (possible 24 hr) for therapy. Moreover, understanding the mechanisms of action of NILT will provide a new therapeutic target for future drug or device development.

Int J Stroke 2008 May 3(2) 88-91

https://www.ncbi.nlm.nih.gov/pubmed/?term=18706001

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Safety Profile of Transcranial Near-Infrared Laser Therapy Administered in Combination With Thrombolytic Therapy to Embolized Rabbits.

Lapchak PA, Han MK, Salgado KF, Streeter J, Zivin JA

From the Department of Neuroscience, University of California San Diego, La Jolla, Calif; the Veterans Administration San Diego Healthcare System, Stroke Research, San Diego, Calif; the Veterans Medical Research Foundation, San Diego, Calif; and Photothera Inc, Carlsbad, Calif..

BACKGROUND AND PURPOSE: Transcranial near-infrared laser therapy (TLT) is currently under investigation in a pivotal clinical trial that excludes thrombolytic therapy. To determine if combining tissue plasminogen activator (tPA; Alteplase) and TLT is safe, this study assessed the safety profile of TLT administered alone and in combination with Alteplase. The purpose for this study is to determine if the combination of TLT and thrombolysis should be investigated further in a human clinical trial. METHODS: We determined whether postembolization treatment with TLT in the absence or presence of tPA would affect measures of hemorrhage or survival after large clot embolism-induced strokes in New Zealand white rabbits. RESULTS: TLT did not significantly alter hemorrhage incidence after embolization, but there was a trend for a modest reduction of hemorrhage volume (by 65%) in the TLT-treated group compared with controls. Intravenous administration of tPA, using an optimized dosing regimen, significantly increased hemorrhage incidence by 160%. The tPA-induced increase in hemorrhage incidence was not significantly affected by TLT, although there was a 30% decrease in hemorrhage incidence in combination-treated rabbits. There was no effect of TLT on hemorrhage volume measured in tPA-treated rabbits and no effect of any treatment on 24-hour survival rate. CONCLUSIONS: In the embolism model, TLT administration did not affect the tPA-induced increase in hemorrhage incidence. TLT may be administered safely either alone or in combination with tPA because neither treatment affected hemorrhage incidence or volume. Our results support the study of TLT in combination with Alteplase in patients with stroke.

Stroke 2008 Aug 7

https://www.ncbi.nlm.nih.gov/pubmed/?term=18687999

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Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light.

Michalikova S, Ennaceur A, van Rensburg R, Chazot PL

University of Sunderland, Sunderland Pharmacy School, Wharncliffe Street, Sunderland SR1 3SD, UK..

Non-thermal near infra-red (IR) has been shown to have many beneficial photobiological effects on a range of cell types, including neurons. In the present study, a pretreatment with a daily 6 min exposure to IR1072 for 10 days yielded a number of significant behavioral effects on middle-aged female CD-1 mice (12-months) tested in a 3D-maze. Middle-aged mice show significant deficits in a working memory test and IR treatment reversed this deficit. Interestingly, the IR treated middle-aged group despite making less memory errors than sham middle-aged group spent longer time in different parts of the maze than both the young group (3-months) and sham-middle-aged group (12-months). Young mice appeared more anxious than middle-aged mice in the first sessions of the test. Exposure to IR appeared to have no significant effects upon exploratory activity or anxiety responses. However, it elicited significant effects on working memory, with the IR middle-aged mice being more considerate in their decision making, which results in an overall improved cognitive performance which is comparable to that of young CD-1 mice. The present study describes a novel method for assessing emotional responses and memory performance in a 3D spatial navigation task and demonstrates the validity of our new all-in-one test and its sensitivity to ageing and non-invasive beneficial IR treatment.

Neurobiol Learn Mem 2008 May 89(4) 480-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=17855128

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[Sucessful therapy of nodular amyloidosis with CO2 laser]

Hodzic-Avdagic N, Diedrichson E, Bruch-Gerharz D, Schulte KW

Hautklinik der Heinrich-Heine-Universitat, Moorenstrasse 5, 40225, Dusseldorf, Germany..

Hautarzt 2007 Oct 58(10) 830, 832-3

https://www.ncbi.nlm.nih.gov/pubmed/?term=17846730

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Transcranial near-infrared light therapy improves motor function following embolic strokes in rabbits: an extended therapeutic window study using continuous and pulse frequency delivery modes.

Lapchak PA, Salgado KF, Chao CH, Zivin JA

University of California San Diego, Department of Neuroscience, MTF 316, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA. plapchak@ucsd.edu.

Photon or near-infrared light therapy (NILT) may be an effective neuroprotective method to reduce behavioral dysfunction following an acute ischemic stroke. We evaluated the effects of continuous wave (CW) or pulse wave (P) NILT administered transcranially either 6 or 12 h following embolization, on behavioral outcome. For the studies, we used the rabbit small clot embolic stroke model (RSCEM) using three different treatment regimens: 1) CW power density of 7.5 mW/cm(2); 2) P1 using a frequency of 300 mus pulse at 1 kHz or 3) P2 using a frequency of 2 ms pulse at 100 Hz. Behavioral analysis was conducted 48 h after embolization, allowing for the determination of the effective stroke dose (P(50)) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the P(50) compared with the control group. Quantal dose-response analysis showed that the control group P(50) value was 1.01+/-0.25 mg (n=31). NILT initiated 6 h following embolization resulted in the following P(50) values: (CW) 2.06+/-0.59 mg (n=29, P=0.099); (P1) 1.89+/-0.29 mg (n=25, P=0.0248) and (P2) 1.92+/-0.15 mg (n=33, P=0.0024). NILT started 12 h following embolization resulted in the following P(50) values: (CW) 2.89+/-1.76 mg (n=29, P=0.279); (P1) 2.40+/-0.99 mg (n=24, P=0.134). At the 6-h post-embolization treatment time, there was a statistically significant increase in P(50) values compared with control for both pulse P1 and P2 modes, but not the CW mode. At the 12-h post-embolization treatment time, neither the CW nor the P1 regimens resulted in statistically significant effect, although there was a trend for an improvement. The results show that P mode NILT can result in significant clinical improvement when administered 6 h following embolic strokes in rabbits and should be considered for clinical development.

Neuroscience 2007 Sep 21 148(4) 907-14

https://www.ncbi.nlm.nih.gov/pubmed/?term=17693028

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Laser treatment for stroke.

Lampl, Y

Edith Wolfson Medical Center, Department of Neurology, Holon, Israel. y_lampl@hotmail.com.

Low-level laser therapy is an irradiation technique that has the ability to induce biological processes using photon energy. There are studies showing proliferation and angiogenesis after irradiation in skeletal muscle post-myocardial infarction tissue cells. Most evidence of efficacy is based on the increase in energy state and the activation of mitochondrial pathways. In the brain, there is similar evidence of cellular activity with laser irradiation. In vivo studies reinforced the efficacy of this technique for a better neurological and functional outcome post-stroke. The evidence is based on in vivo animal studies of various models and one human clinical study. Although the data is very promising, some fundamental questions remain to be answered, such as the exact mechanism along the cascade of post-stroke interconnective molecular disturbance, the optimal technique and time of treatment, and the long-term safety aspects. The answers to these questions are expected to evolve within the next few years.

Expert Rev Neurother 2007 Aug 7(8) 961-5

https://www.ncbi.nlm.nih.gov/pubmed/?term=17678491

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[Correction of free-radical processes in patients with chronic brain ischemia with intravenous laser irradiation of blood]

Karneev AN, Solov’eva EIu, Fedin AI

We examined lipid peroxidation (LPO) in 130 patients with chronic brain ischemia (CBI). Primary and secondary LPO products, oxidative and antioxidative enzymes were studied in the course of therapy with antioxidant drug cytoflavin and intravenous laser radiation of blood (ILRB). The latter proved to have a normalizing action on LPO and antioxidant defense. With progression of CBI, effects of ILRB on enzymatic activity weakens due to depletion of endogenic antioxidants. This necessitates administration of exogenic antioxidants (cytoflavin) for complex correction of free radical processes. This conclusion allows recommending combined schemes of therapy for patients with CBI stage II and III.

Vopr Kurortol Fizioter Lech Fiz Kult 2007 May-Jun -3 38524

https://www.ncbi.nlm.nih.gov/pubmed/?term=17645076

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Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1).

Lampl Y, Zivin JA, Fisher M, Lew R, Welin L, Dahlof B, Borenstein P, Andersson B, Perez J, Caparo C, Ilic S, Oron U

Wolfson Medical Center, Department of Neurology, Holon, Israel..

BACKGROUND AND PURPOSE: The NeuroThera Effectiveness and Safety Trial-1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke. METHODS: This was a prospective, intention-to-treat, multicenter, international, double-blind, trial involving 120 ischemic stroke patients treated, randomized 2:1 ratio, with 79 patients in the active treatment group and 41 in the sham (placebo) control group. Only patients with baseline stroke severity measured by National Institutes of Health Stroke Scale (NIHSS) scores of 7 to 22 were included. Patients who received tissue plasminogen activator were excluded. Outcome measures were the patients’ scores on the NIHSS, modified Rankin Scale (mRS), Barthel Index, and Glasgow Outcome Scale at 90 days after treatment. The primary outcome measure, prospectively identified, was successful treatment, documented by NIHSS. This was defined as a complete recovery at day 90 (NIHSS 0 to 1), or a decrease in NIHSS score of at least 9 points (day 90 versus baseline), and was tested as a binary measure (bNIH). Secondary outcome measures included mRS, Barthel Index, and Glasgow Outcome Scale. Primary statistical analyses were performed with the Cochran-Mantel-Haenszel rank test, stratified by baseline NIHSS score or by time to treatment for the bNIH and mRS. Logistic regression analyses were conducted to confirm the results. RESULTS: Mean time to treatment was >16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%), as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days as a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS (“shift in Rankin”) score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs). CONCLUSIONS: The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.

Stroke 2007 Jun 38(6) 1843-9

https://www.ncbi.nlm.nih.gov/pubmed/?term=17463313

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[Effect of magnet-laser therapy on the central nervous system functional state in patients with ischemic stroke]

Datsenko, IV

Twenty three patients aged from 41 to 75, which have had ischemic stroke in the carotid basin (up to 2 years after an acute period of the stroke), have been examined. The course of magneto-laser therapy lasted 15 days. The author carried out neurological examinations, determined the state of psychoemotional activity, cerebral hemodynamics and frequency-amplitude indices of the brain to assess the mechanisms of MLT effect on the CNS functional state in patients being in a rehabilitative period after ischemic stroke. The course of MLT administration improves cerebral hemodynamics, increases the level of the bioelectrical activity of the brain. We can recommend based on obtained results MLT in the system of rehabilitation of patients which had had ischemic stroke.

Lik Sprava 2006 Apr-May -3 51-4

https://www.ncbi.nlm.nih.gov/pubmed/?term=17100186

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Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits.

Oron A, Oron U, Chen J, Eilam A, Zhang C, Sadeh M, Lampl Y, Streeter J, DeTaboada L, Chopp M

Department of Orthopedics, Assaf Harofeh Medical Center, Zerifin 70300, Israel. amiroronmd@gmail.com.

BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue. METHODS: Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2. RESULTS: In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT. CONCLUSIONS: Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.

Stroke 2006 Oct 37(10) 2620-4

https://www.ncbi.nlm.nih.gov/pubmed/?term=16946145

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Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain.

Ilic S, Leichliter S, Streeter J, Oron A, DeTaboada L, Oron U

Photothera Inc., Carlsbad, California, USA..

OBJECTIVE: The aim of the present study was to investigate the possible short- and long-term adverse neurological effects of low-level laser therapy (LLLT) given at different power densities, frequencies, and modalities on the intact rat brain. BACKGROUND DATA: LLLT has been shown to modulate biological processes depending on power density, wavelength, and frequency. To date, few well-controlled safety studies on LLLT are available. METHODS: One hundred and eighteen rats were used in the study. Diode laser (808 nm, wavelength) was used to deliver power densities of 7.5, 75, and 750 mW/cm2 transcranially to the brain cortex of mature rats, in either continuous wave (CW) or pulse (Pu) modes. Multiple doses of 7.5 mW/cm2 were also applied. Standard neurological examination of the rats was performed during the follow-up periods after laser irradiation. Histology was performed at light and electron microscopy levels. RESULTS: Both the scores from standard neurological tests and the histopathological examination indicated that there was no long-term difference between laser-treated and control groups up to 70 days post-treatment. The only rats showing an adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal dose), CW mode group. In Pu mode, there was much less heating, and no tissue damage was noted. CONCLUSION: Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as well as at multiple doses at the same power densities, indicate that the tested laser energy doses are safe under this treatment regime. Neurological deficits and histopathological damage to 750 mW/cm2 CW laser irradiation are attributed to thermal damage and not due to tissue-photon interactions.

Photomed Laser Surg 2006 Aug 24(4) 458-66

https://www.ncbi.nlm.nih.gov/pubmed/?term=16942425

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Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke.

Detaboada L, Ilic S, Leichliter-Martha S, Oron U, Oron A, Streeter J

Photothera, Inc., 2260 Rutherford Road, Carlsbad, California 92008, USA..

BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to have beneficial effects on ischemic skeletal and heart muscles tissues. The aim of the present study was to approve the effectiveness of LLLT treatment at different locations on the brain in acute stroked rats. STUDY DESIGN/MATERIALS AND METHODS: Stroke was induced in 169 rats that were divided into four groups: control non-laser and three laser-treated groups where laser was employed ipsilateral, contralateral, and both to the side of the induced stroke. Rats were tested for neurological function. RESULTS: In all three laser-treated groups, a marked and significant improvement in neurological deficits was evident at 14, 21, and 28 days post stroke relative to the non-treated group. CONCLUSIONS: These observations suggest that LLLT applied at different locations in the skull and in a rather delayed-phase post stroke effectively improves neurological function after acute stroke in rats.

Lasers Surg Med 2006 Jan 38(1) 70-3

https://www.ncbi.nlm.nih.gov/pubmed/?term=16444697

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[Increases of intracranial pressure and changes of blood flow velocity due to acupressure, needle and laser needle acupuncture?]

Litscher G, Wang L, Schwarz G, Schikora D

Biomedizintechnische Forschung in Anasthesie und Intensivmedizin, Medizinische Universitat Graz, Osterreich. gerhard.litscher@meduni-graz.at.

BACKGROUND: Pressure on the acupoints St.7 and SJ.22 can lead to significant, reversible increases in intracranial pressure (ICP) in patients with elevated ICP. OBJECTIVE: In this study, we investigated whether changes in cerebral parameters in healthy volunteers can also be registered, when the mentioned acupoints associated with ICP, are stimulated. SUBJECTS AND METHODS: We investigated a total of 34 volunteers (24 females, 10 males) and a 15-year-old intensive care patient after severe head injury. The mean age of volunteers was 25.2 +/- 3.4 years (range 20-35). Stimulation was performed using acupressure techniques, manual needle and laser needle methods. We evaluated the main parameter of mean blood flow velocity in the middle cerebral artery (left and right) as well as the pulsatility index. In addition, near infrared spectroscopy and blood pressure parameters were registered. RESULTS: Acupressure, manual needle acupuncture and laser needle acupuncture partially led to significant changes in the main goal values. CONCLUSION: Acupressure as well as acupuncture (needle and laser needle) can evoke reproducible functional changes in the brain. These accompanying effects are not to be ignored, in particular in patients with increased ICP.

Forsch Komplementarmed Klass Naturheilkd 2005 Aug 12(4) 190-5

https://www.ncbi.nlm.nih.gov/pubmed/?term=16137980

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Mechanisms of action of light therapy for stroke and acute myocardial infarction.

Streeter J, De Taboada L, Oron U

Photothera, Inc., 2260 Rutherford Road, Suite 101, Carlsbad, CA 92008, USA. jstreeter@photothera.com.

Mitochondrion 2004 Sep 4(5-6) 569-76

https://www.ncbi.nlm.nih.gov/pubmed/?term=16120415

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[Protective effect of low-level laser irradiation on acupuncture points combined with iontophoresis against focal cerebral ischemia-reperfusion injury in rats]

Dai JY, Ge LB, Zhou YL, Wang L

Acupuncture Clinic, Institute of Qigong, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China. djysh2002@yahoo.com.cn.

OBJECTIVE: To investigate the effects of low-level laser irradiation on acupuncture points combined with iontophoresis against brain damage after middle cerebral artery occlusion (MCAO) in rats. METHODS: Sixty-nine SD rats were randomly divided into five groups, including normal group, sham operation group, model group, electro-acupuncture group and low-level laser irradiation on acupuncture points combined with iontophoresis group (LLLI group). The cerebral ischemia-reperfusion (I/R) model was established by thread embolism of middle cerebral artery. The rats in the LLLI group, as well as the electro-acupuncture group were given treatment as soon as the occlusion finished (0 hour) and 12, 24 hours after the occlusion. We observed the changes of neurological deficit scores and the body weight of the rats at different time. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ratos brain tissue were tested. RESULTS: The neurological deficit score of the LLLI group was significantly lower than that of the model group. The body weight and the activity of SOD of the rats decreased slightly, and the content of MDA decreased significantly after the treatment. CONCLUSION: The low-level laser irradiation on acupuncture points combined with iontophoresis can prevent focal cerebral ischemia-reperfusion injury. One of its mechanisms may be increasing the activity of SOD and decreasing the damage of the oxidation products to the body.

Zhong Xi Yi Jie He Xue Bao 2005 Mar 3(2) 128-31

https://www.ncbi.nlm.nih.gov/pubmed/?term=15763061

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Efficiency of laser therapy applied in labial traumatism of patients with spastic cerebral palsy.

Moreira LA, Santos MT, Campos VF, Genovese WJ

Laser Disciplines in Dentistry, Implantodontics and Integrated Dentistry Clinic, University of Cruzeiro do Sul (UNICSUL), Sao Paulo, SP, Brazil. lam@apcd.org.br.

The aim of this study was to report the effectiveness of laser therapy applied to traumatic labial injury of patients with spastic cerebral palsy. We report two cases of patients with internal mucosa and lower lip traumatism caused by oral reflex automatism with spastic tonic bite and lower lip interposition. One patient presented extensive lower lip ulceration, loss of tissue, crusty and hemorrhagic areas, with increasing pain and spasticity. The other patient presented local congestion signs, extremely enlarged tissue growth and increased labial volume. Laser therapy was applied to all injured areas, with a low-potency diode InGaAlP laser [685 nm Quasar (Dentoflex), 190 J/ cm2, with a 24-h interval between the first and second administration, and a 7-day interval between the two subsequent ones. At first re-evaluation, 24 h later, there was a striking reduction in inflammation, a decrease in vascular congestion, and a reduction of the ulcerated area with spasticity and pain reduction. At the 14-day re-evaluation, significant clinical differences in the advanced healing process were seen. Low-intensity laser showed to be effective in traumatic soft tissue treatment in cerebral palsy patients by accelerating the healing process, reducing secondary contamination, promoting analgesia; thus, it can be an important tool in the treatment of these patients.

Braz Dent J 2004 15 Spec No SI29-33

https://www.ncbi.nlm.nih.gov/pubmed/?term=15690768

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Transcranial infrared laser therapy improves clinical rating scores after embolic strokes in rabbits.

Lapchak PA, Wei J, Zivin JA

Department of Neuroscience, University of California San Diego, MTF 316, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA. plapchak@ucsd.edu.

BACKGROUND AND PURPOSE: Because photon energy delivered using a low-energy infrared laser may be useful to treat stroke, we determined whether transcranial laser therapy would improve behavioral deficits in a rabbit small clot embolic stroke model (RSCEM). METHODS: In this study, the behavioral and physiological effects of laser treatment were measured. The RSCEM was used to assess whether low-energy laser treatment (7.5 or 25 mW/cm2) altered clinical rating scores (behavior) when given to rabbits beginning 1 to 24 hours postembolization. Behavioral analysis was conducted from 24 hours to 21 days after embolization, allowing for the determination of the effective stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the P50 compared with the control group. RESULTS: In the present study, the P50 value for controls were 0.97+/-0.19 mg to 1.10+/-0.17 mg; this was increased by 100% to 195% (P50=2.02+/-0.46 to 2.98+/-0.65 mg) if laser treatment was initiated up to 6 hours, but not 24 hours, postembolization (P50=1.23+/-0.15 mg). Laser treatment also produced a durable effect that was measurable 21 days after embolization. Laser treatment (25 mW/cm2) did not affect the physiological variables that were measured. CONCLUSIONS: This study shows that laser treatment improved behavioral performance if initiated within 6 hours of an embolic stroke and the effect of laser treatment is durable. Therefore, transcranial laser treatment may be useful to treat human stroke patients and should be further developed.

Stroke 2004 Aug 35(8) 1985-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=15155955

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[Biochemical and immunological induces of the blood in Parkinson’s disease and their correction with the help of laser therapy]

Komel’kova LV, Vitreshchak TV, Zhirnova IG, Poleshchuk VV, Stvolinskii SL, Mikhailov VV, Gannushkina IV, Piradov MA

The influence of laser therapy on the course of Parkinson’s disease (PD) was studied in 70 patients. This influence appeared adaptogenic both in the group with elevated and low MAO B and Cu/Zn SOD activity. Laser therapy resulted in reduction of neurological deficit, normalization of the activity of MAO B, Cu/Zn-SOD and immune indices. There was a correlation between humoral immunity and activity of the antioxidant enzymes (SOD, catalase). This justifies pathogenetically the use of laser therapy in PD.

Patol Fiziol Eksp Ter 2004 Jan-Mar -1 38578

https://www.ncbi.nlm.nih.gov/pubmed/?term=15052871

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[Magnetic and laser therapy of acute ischemic stroke]

Samosiuk, NI

The paper presents the technique of frequency-modulated magnetolaser therapy (FMMLT) used in combined treatment of 121 patients with ischemic stroke in acute period. The results were compared with those in the control group of 30 patients who received conventional drug treatment. The results of the comparison allowed the author to recommend FMMLT in ischemic stroke especially in the period of “therapeutic window”.

Vopr Kurortol Fizioter Lech Fiz Kult 2003 Mar-Apr (2) 19-20

https://www.ncbi.nlm.nih.gov/pubmed/?term=12924186

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Laser modification of the blood in vitro and in vivo in patients with Parkinson’s disease.

Vitreshchak TV, Mikhailov VV, Piradov MA, Poleshchuk VV, Stvolinskii SL, Boldyrev AA

Institute of Neurology of the Russian Academy of Medical Sciences, Moscow..

The effect of He-Ne laser radiation on activity of MAO B, Cu/Zn-SOD, Mn-SOD, and catalase in blood cells from patients with Parkinson’s disease was studied in vivo and in vitro. The effects of intravenous in vivo irradiation (intravenous laser therapy) were more pronounced than those observed in similar in vitro experiments. It is concluded that generalized effect of laser therapy involves interaction between blood cells.

Bull Exp Biol Med 2003 May 135(5) 430-2

https://www.ncbi.nlm.nih.gov/pubmed/?term=12910278

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Comparison of a short irradiation (50 sec) by different wavelengths on audiogenic seizures in magnesium-deficient mice: evidence for a preventive neuroprotective effect of yellow.

Pages N, Bac P, Maurois P, Durlach J, Agrapart C

Laboratoire de Toxicologie, Faculte de Pharmacie, Strasbourg, 67400 Illkirch Graffenstaden, France. nicole.pages4@wanadoo.fr.

Audiogenic seizures triggered by an acoustic stimulus of determined frequency and amplitude have been described in many laboratory animals in many circumstances including magnesium deficiency. This model, recently validated, was used, in DBA/2 mice, to study the preventive neuroprotective effect of 6 wavelengths of the visible spectrum used in Chromatotherapia* (lambda(max) 440, 484, 528, 572, 616 and 660 nm) at low irradiance. Each short illumination lasted 50 seconds and was followed by 20 minutes of darkness. It appeared that yellow fully protected 16 out of 17 mice from seizure occurrence. Green allowed the survival of 69% of mice but did not protect them from seizure occurrence. On the contrary, the other four colors (orange, red, purple and blue) failed to protect the mice and showed a tendency to accelerate their death. White color was not protective but allowed the difficult survival of 30% of mice. Darkness had no protective effect. These results even though surprising open a great field of investigation.

Magnes Res 2003 Mar 16(1) 29-34

https://www.ncbi.nlm.nih.gov/pubmed/?term=12735480

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Treatment of experimentally induced transient cerebral ischemia with low energy laser inhibits nitric oxide synthase activity and up-regulates the expression of transforming growth factor-beta 1.

Leung MC, Lo SC, Siu FK, So KF

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, The University of Hong Kong, Hong Kong. rsmcpleung.edu.hk.

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been shown to be neurotoxic while transforming growth factor-beta 1 (TGF-beta1) is neuroprotective in the stroke model. The present study investigates the effects of low energy laser on nitric oxide synthase (NOS) and TGF-beta1 activities after cerebral ischemia and reperfusion injury. STUDY DESIGN/MATERIALS AND METHODS: Cerebral ischemia was induced for 1 hour in male adult Sprague-Dawley (S.D.) rats with unilateral occlusion of middle cerebral artery (MCAO). Low energy laser irradiation was then applied to the cerebrum at different durations (1, 5, or 10 minutes). The activity of NOS and the expression of TGF-beta1 were evaluated in groups with different durations of laser irradiation. RESULTS: After ischemia, the activity of NOS was gradually increased from day 3, became significantly higher from day 4 to 6 (P < 0.001), but returned to the normal level after day 7. The activity and expression of the three isoforms of NOS were significantly suppressed (P < 0.001) to different extents after laser irradiation. In addition, laser irradiation was shown to trigger the expression of TGF-beta1 (P < 0.001). CONCLUSIONS: Low energy laser could suppress the activity of NOS and up-regulate the expression of TGF-beta1 after stroke in rats.

Lasers Surg Med 2002 31(4) 283-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=12355575

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Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue.

Mochizuki-Oda N, Kataoka Y, Cui Y, Yamada H, Heya M, Awazu K

Institute of Free Electron Laser, Graduate School of Engineering, Osaka University, Hirakata, Osaka 573-0128, Japan. oda@fel.eng.osaka-u.ac.jp.

Low-power, near-infra-red laser irradiation has been used to relieve patients from various kinds of pain, though the precise mechanisms of such biological actions of the laser have not yet been resolved. To investigate the cellular mechanisms by near-infra-red laser on the nervous system, we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area, whereas the adenosine diphosphate (ADP) content showed no significant difference. Laser irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the tissue was increased by 4.4-4.7 degrees C during the irradiation of both wavelengths. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from a specific effect of the laser operated at the 830-nm wavelength.

Neurosci Lett 2002 May 3 323(3) 207-10

https://www.ncbi.nlm.nih.gov/pubmed/?term=11959421

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[The effect of intravenous laser irradiation of the blood on the brain bioelectrical activity in patients in the postcomatose period]

Idrisova LT, Enikeev DA, Vasil’eva TV

The article presents clinical data on therapeutic effects of intravenous laser blood irradiation (BI) in severe alcohol intoxication complicated by alcohol coma. BI effectiveness was assessed by EEG changes within 3 postcomatose days. Changes in brain biopotentials in various postcomatose periods were unidirectional. Positive results were achieved after low-intensity laser radiation.

Vopr Kurortol Fizioter Lech Fiz Kult 2000 Mar-Apr -2 28-31

https://www.ncbi.nlm.nih.gov/pubmed/?term=11094892

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[The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy]

Kochetkov AV, Gorbunov FE, Minenkov AA, Strel’tsova EN, Filina TF, Krupennikov AI

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

Vopr Kurortol Fizioter Lech Fiz Kult 2000 May-Jun -3 17-21

https://www.ncbi.nlm.nih.gov/pubmed/?term=10925665

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Phospholipid pool, lipid peroxidation, and superoxide dismutase activity under various types of oxidative stress of the brain and the effect of low-energy infrared laser irradiation.

Karageuzyan KG, Sekoyan ES, Karagyan AT, Pogosyan NR, Manucharyan GG, Sekoyan AE, Tunyan AY, Boyajyan VG, Karageuzyan MK

Institute of Molecular Biology, National Academy of Sciences of Armenia, Erevan, 375014, Armenia. gkarine@pnas.sci.am.

The effect of low-energy infrared laser irradiation on the phospholipid pool, lipid peroxidation, and superoxide dismutase activity in the brain of white rats was studied in experimental ischemia, reperfusion, and acute edema. These models are characterized by oxidative stress; the contents of tri- and diphosphoinositides and sphingomyelins were lowered, whereas the levels of phosphatidylserine and phosphatidylethanolamine did not change, and the amount of phosphatidylcholine was increased. In acute brain edema, the contents of hydroperoxides and malonic dialdehyde in enzymatic and nonenzymic lipid peroxidation systems were increased in mitochondrial and microsomal fractions and the level of arachidonic acid was significantly elevated. Infrared laser irradiation contributes to the correction of the changes in the phospholipid pool; laser irradiation lowered the increased levels of hydroperoxides and malonic dialdehyde and elevated superoxide dismutase activity in the brain during ischemia, reperfusion, and acute edema of the brain. The data suggest that low-energy infrared laser irradiation has certain neuroprotective activity in various types of oxidative stress including ischemia, reperfusion, and acute edema of the brain.

Biochemistry (Mosc) 1998 Oct 63(10) 1226-32

https://www.ncbi.nlm.nih.gov/pubmed/?term=9864460

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In vitro cellular processes sprouting in cortex microexplants of adult rat brains induced by low power laser irradiation.

Wollman Y, Rochkind S

Department of Nephrology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel..

The effect of He-Ne low power laser irradiation on the growth of cellular processes of microexplants of the brain cortex of adult rats in tissue culture was studied. Two 8-min doses of direct laser irradiation, 3.6 J/cm2 each given on two successive days, caused a significant amount of sprouting of cellular processes outgrowth in microexplants compared to small amounts produced by nonirradiated controls. This preliminary observation suggests that low power laser irradiation applied to the area of an experimentally injured nerve may induce neurite processes sprouting, thereby improving nerve tissue recovery.

Neurol Res 1998 Jul 20(5) 470-2

https://www.ncbi.nlm.nih.gov/pubmed/?term=9664597

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Neurological rehabilitation: acupuncture and laser acupuncture to treat paralysis in stroke, other paralytic conditions, and pain in carpal tunnel syndrome.

Naeser, MA

Department of Neurology, Boston University School of Medicine, Massachusetts, USA..

J Altern Complement Med 1997 Winter 3(4) 425-8

https://www.ncbi.nlm.nih.gov/pubmed/?term=9449066

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[The neuromotor functional status of patients with circulatory encephalopathy]

Ivaniv AP, Shmakova IP

The aim of this study was to reveal the secondary neuromuscular disorders in 104 patients with spondylogenic discirculatory encephalopathy and to study the influence of different methods of combined physiotherapy (laser irradiation, troxevasin vacuum-phonophoresis, vacuum-message) on dynamics of electroneuromyographic (ENMG) indices. The application of electroneuromyography (ENMGST-01 apparatus) permitted to establish that pathological neurophysiological phenomena developed in patients progrediently and were qualitatively unstable. It was also determined that combined usage of laser-photobiostimulation and troxevasin vacuum-phonophoresis promoted more steadfast liquidation of neurological signs of the disease as well as the improvement of functional state of neuromotor system. Moreover, the usage of combined ENMG methods significantly contributed to understanding of pathological processes underlying the evaluated neurophysiological syndromes. The authors made the conclusion about high effectiveness and good perspectives of craniocaudal coefficient’s application for determination of correlations between clinical state of patients and diagnostic tests’ data.

Zh Nevrol Psikhiatr Im S S Korsakova 1996 96(4) 63-6

https://www.ncbi.nlm.nih.gov/pubmed/?term=9281282

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[Low-energy He-Ne-laser-induced neurochemical changes during brain ischemia/reperfusion and their integral estimation using a factor analysis model]

Karagezian KG, Sekoian ES, Boiadzhian VG, Manucharian GG, Ordukhanian AA, Sekoian AE, Danielian RK

Dokl Akad Nauk 1996 Oct 350(6) 837-41

https://www.ncbi.nlm.nih.gov/pubmed/?term=8998457

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Low power laser irradiation reduces ischemic damage in hippocampal slices in vitro.

Iwase T, Hori N, Morioka T, Carpenter DO

Department of Pharmacology, Kyushu University School of Dentistry, Fukuoka, Japan..

BACKGROUND AND OBJECTIVE: Low power laser irradiation has been reported to reduce injury, promote regeneration, and produce analgesia. While the mechanism is unknown, one hypothesis is that light produces free radicals, which have a beneficial effect at low concentrations. STUDY DESIGN/MATERIALS AND METHODS: We have investigated the effects of low power laser irradiation on the loss of electrical excitability of hippocampal brain slices after a transient exposure to a perfusion medium lacking oxygen and containing reduced glucose concentrations. Injury in this system is known to result at least in part from free radical production. RESULTS: Low power laser irradiation increased the time required for loss of excitability and increased recovery from the ischemic injury. CONCLUSIONS: Low power laser irradiation has acute protective effects against ischemic damage in brain slices.

Lasers Surg Med 1996 19(4) 465-70

https://www.ncbi.nlm.nih.gov/pubmed/?term=8983008

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Low power laser irradiation enhances migration and neurite sprouting of cultured rat embryonal brain cells.

Wollman Y, Rochkind S, Simantov R

Department of Nephrology, Ichilov Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Israel..

We used fetal brain cells grown in tissue culture to study some basic features of the interaction between low-power laser irradiation and biological systems. Seven- to nine-day-old rat fetal brain cell aggregates in culture were subjected to direct focused irradiation of low-power helium-neon laser (0.3 mW, 632.8 nm). An 8-minute dose of laser irradiation enhanced the appearance of brain cells around the treated aggregates, as monitored under the microscope of the stained cultures. Two and three doses of laser irradiations were correlated with 97% and 142% respective increases of the numbers of cells surrounding the aggregates. To identify the type of cells grown in the outgrowth of the treated aggregate, specific tetanus-anti-tetanus antibodies were used. Rhodamine-labeled antibodies bound to receptors on cells indicated massive neurite sprouting and outgrowth of migrating brain cells in culture.

Neurol Res 1996 Oct 18(5) 467-70

https://www.ncbi.nlm.nih.gov/pubmed/?term=8916064

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The current significance of physiotherapeutic measures in the treatment of Parkinson’s disease.

Ulm, G

Paracelsus-Elena Clinic, Kassel, Federal Republic of Germany..

Physical measures as adjuvant therapy in Parkinson’s disease have so far received insufficient investigation from the viewpoint of either their clinical effectiveness or of their theoretical rationale, although they are widely prescribed in practice and contribute a substantial cost factor to the overall treatment. Most attention has been devoted to movement therapy, which may admittedly only achieve minor improvements in motor performance but contributes substantially to subjective improvement of the well-being of the patients and to the maintenance of their physiological functions. Speech therapy seems to be effective only for patients who are highly motivated and have not suffered any psychological deficits and who continue exercising on their own. Massage, ergonomic treatment approaches and the nowadays fashionable area of various relaxation techniques have received very little attention. Our own trials with vibro-massage (swing-exbusar) for the loosening of muscular rigidity have led to no sustained improvement, and our attempts to improve speech defects in Parkinsonian patients by the application of laser acupuncture have likewise not resulted in improvement.

J Neural Transm Suppl 1995 46 455-60

https://www.ncbi.nlm.nih.gov/pubmed/?term=8821081

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[The magneto-, photo- and laser therapy of headaches in patients with vascular brain lesions]

Troshin VD, Miasnikov IG, Belousova TE

To manage vascular cephalalgia, a combined approach is proposed: segmentally oriented magnetic, photo- and photomagnetic therapy plus intravenous laser treatment. The effect was directly correlated with cerebral hemodynamic condition, damage to vegetative innervation segmental-peripheral link and physiotherapeutic factors.

Zh Nevrol Psikhiatr Im S S Korsakova 1994 94(5) 38578

https://www.ncbi.nlm.nih.gov/pubmed/?term=7900442

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[Therapeutic efficacy of laser and electropuncture reflexotherapy in correcting the initial manifestations of cerebral circulatory insufficiency]

Nikolaev, NA

Electrical and laser acupuncture was used in 2 groups of 50 patients each who presented initial manifestations of cerebral circulation insufficiency (CCI). It was shown that stimulating an experimentally selected combination of acupuncture points on the affected side in initial manifestations of CCI, it was possible to achieve a regionally localized action correcting the cerebral hemodynamics. Changes in the tone of the regional vessels of the brain were objectively documented with the help of echopulsography of the cerebral vessels. The findings obtained included prolongation of the blood clotting time, a decreased index of thrombin inactivation and a reduction in the spontaneous fibrinolytic activity of the blood.

Zh Nevropatol Psikhiatr Im S S Korsakova 1986 86(1) 60-4

https://www.ncbi.nlm.nih.gov/pubmed/?term=3953196

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[Laser therapy of post-stroke Dejerine-Roussy thalamic syndrome]

Anishchenko GIa, Pisareva GI, Kochetkov VD

Sov Med 1986 -4 41-3

https://www.ncbi.nlm.nih.gov/pubmed/?term=3715607

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APPLICATION OF LOW REACTIVE-LEVEL LASER THERAPY (LLLT) IN PATIENTS WITH CEREBRAL PALSY OF THE ADULT TENSION ATHETOSIS TYPE

Yoshimi Asagail, Ryuichi Uenol, Yukio Miura, Toshio Ohshiro

1: Shinano Handicapped Children’s Hospital, Shimosuwa, Nagano,2: Department of Orthopaedic Surgery, Tokyo Medical College, Shinjuku, Tokyo; and 3: Japan Medical Laser Laboratory, Shinanomachi, Tokyo, Japan.

In patients with cerebral palsy of the tension athetosis type, a number of symptoms may be observed, including not only the fairly constant involuntary athetotic movements but also myotonic disorders of the motor function of all four limbs and trunk, vocalization and motions associated with eating such as mastication and swallowing. Aggravation of involuntary movements and pain in the neck and back are also seen in many cases. Existing conservative treatment methodologies have proved to be more or less ineffective, and limitations in functional training in adults have made treatment extremely difficult. We first employed low reactive-level laser therapy (LLLT) in a case of spastic cerebral palsy in 1994 with good results. In the present study, we applied laser irradiation (830 nm. 60 mW continuous wave) to all myotonic sites around the face and neck region where myotonia was severe in 20 patients with cerebral palsy of the adult tension athetosis type for which there was no effective treatment for their neck and back pain. Improvement of myotonia was seen in 19 patients while improvement of pain in the neck and back was seen in all the 16 patients who had pain in these regions. Suppression of myotonia reduced tonic vocalization making words easily heard; more- over, suppression of myotonia and involuntary movements improved working efficiency enabling the patient to perform fairly complex tasks such as word processing. Insomnia and dysuria also improved. Even in the most severe cases, assisting the patient became easier and breathing improved. LLLT with the 830 nm diode laser provides a new and effective treatment modality in this extremely problematic condition, has no serious side effects, and has the potential to improve these patients’ quality of life.

Key words: Low reactive-level laser therapy, cerebral palsy, adult tension athetosis type, rehabilitation, pain attenuation, functional trainingp

Introduction We have reported that low reactive-level laser therapy (LLLT) suppressed tonic muscle spasm in children with spastic cerebral palsy and improved the efficiency of their ftinctional training.(I,2) Pain of the neck and back is often observed in patients with cerebral palsy of the Addressee for Correspondence: Yoshimi Asagai MD, Director, Shinano Handicapped Children’s Hospital, 6525-1 Shimosuwa, Suwagun, Nagano, Japan 393 adult tension athetosis type and at present there is no really effective conservative conventional therapy. In-deed some treatment methods result in aggravation of the involuntary constant slow writhing movements associated with athetosis, and the pain caused by in- creased myotonia. We have used ULT in patients affected by this disease to suppress neck and back pain as well as systemic myotonia since 1994, and obtained Manuscript received:june, 1995 Accepted for publication: September, 1995 good results. The present study will present repre- sentative case reports.

Subjecits and Methods Subjects: The subjects were 20 patients with cerebral palsy of the tension athetosis type (mean age: 32 years; range: 20-53 years). Neck and back pain was seen in 16 cases. As for their motor function level, 1 1 patients could walk while the others were unable to walk and were relied entirely on assistance for their daily life; Three from this latter group could not even hold themselves in the sitting position. Laser: The laser apparatus used was a GaAlAs diode laser, (OhILase-3DI, Prolijapan: 830 nm, 6OmW output and continuous wave) (Figure 1). Referring to Ohshiro’s proximal priority method@3) in which treatment is applied from the proximal to distal areas, relevant acupuncture points, nerve block sites and muscle tendons showing severe myotonia were irradiated for 30 seconds at a time, for 15 to 30 minutes in total while placing emphasis in treating the face and neck regions where myotonia was observed from the centre out to the periphery (Figure 2). Direct irradiation of the eye or irradiation of non-myotonic sites was avoided. The laser was applied in the contact method with mild pressure to increase the penetration capabilities of the 830 nm beam by compressing out the superficial microvasculature. Laser irradiation was performed once a week for outpatients or every day for a period of 2 weeks to I month for I I inpatients, and was delivered together with functional training. The longest period of irradiation was 1 year and 6 months. Before and at the end of treatment, voluntary movements were recorded on videotape, the patient’s pain score and the R-R interval (i.e. the elapsed time between two QRS complexes) on electrocardiograms were determined, and thermogra-phy and facial electromyography were carried out. Resulits Systemic myotonia was suppressed after irradiation in 19 patients, and neck and back pain ameliorated in the 16 patients who had been suffering from pain. If the pain score before irradiation was set at 10 points, the score after irradiation was between 0 and 3 in 6 inpatients who showed excellent effects, between 4 and 7 in 2 inpatients and 6 outpatients who showed good effects and between 8 and 9 in 2 outpatients in whom the LLLT was graded as minimally effective (Table 1). No patient failed to show even slight improvement or got any worse. In 2 patients who were followed up over a long period, although the therapy was extremely effective during hospitalization, the ‘excellent’ efficacy of the Fig 1: The Oh Lase-3DI diode laser therapy unit. The easy-to-hold handpiece is connected to the control console by aflexible cable. Table 1: Evaluation of treatment based on decrease of pain score in 16 patients with bad pain. Inpatients Outpatients Pain score n=8 n=8 Extremely effective: 6 0 0-3 Effective: 2 6 4-7 Slightly effective: 8-9 0 2 Table 2: Improvement of symptoms after LLLT. No. of Symptom patients Systemic suppression of myotonia 18 Improvement of pain 15 Warming of the whole body 12 Prolongation of vocalization time (im- 8 provement of language disorder) Improvement of asymmetric posture 8 Improvement of activities of daily living 5 Improvement of insomnia 4 Improvement of dysuria, constipation, working ability of the upper limbs and 2 involuntary movements Reduction of the oral dose of muscular relaxant, and improvement in difficul- 1 ties associated with opening of the mouth treatment lasted for only 2 or 3 days after irradiation after which patient became an outpatient, gradually returning to the pretreatment condition. Pain increased again after 1 month following the conclusion of the first therapy period whereafter the patients were hospitalized for a second time. Following the retreatment, improvement of myotonia and pain, mainly while warming of the whole body, was seen in 12 patients, prolongation of vocalization time in 8, and improvement of asymmetric posture in 8 (Table 2). Two patients, one in whom evaluation of the efficacy of therapy was difficult due to marked mental retardation and another who could not hold himself in the sitting position due to severe suppression of myotonia, did not wish to undergo a second session of LUT. The effects of LLLT lasted for from 2-3 hours to 1 week and the duration was prolonged by 2-4 days at the longest by continuous irradiation. Thermography was performed in 7 patients. Skin temperature in the face, trunk and upper limbs rose 2’C – 7’C in three of the seven while in two others, whole body warming was seen. The temperature increase lasted for more than 1 hour (Figure 3: see together with Figure 8 on page 117). The remaining two patients in whom the temperature did not rise after the initial irradiation session also showed a rise of skin temperature after I month of continuous irradiation. The R-R interval determined by electrocardiography was used to evaluate autonomic nerve function. A decrease in the standard deviation of the R-R interval and coefficient of variance were observed in 5 cases and s Facial, thor Suprascapular 9 ominal Pron ertebral teres es mu Addu ohkoku musc acupuncture point Inpoh amstrings acupunctur bial nerve point Posterior tibial muscle Peroneus longus Achilles tendon and brevis muscles Fig 2: Schema of LLLT target points. All the regions with myotonia, especially in the face, neck and back, were irradiated. the effect on the autonomic nervous sys mw tem as indicated by these data was suggested as part of the action mechanisms of the diode laser LLLT. The only side effects seen were temporary aggravation of posture maintenance due to severe suppression of b myotonia in 2 cases and asthenia in 3 cases, but no serious side effects were observed. Case Reports Case 1: 31 year old female (Figure 4): This patient was hospitalized so that she could receive continuous LLLT and funcc A6 ea tional training. Her neck and back pain Fig 4: A 31 year-old female patient with cerebral palsy of the tension athetosis type. improved; extreme rotation of the right (a,b): Before LLLT. (c,d): After LLLT. ULT and functional training were given side and involuntary movements, rL every day for I month. Neck and back pain as well as involuntary movements in the face and neck were improved. corded as occurring approximately 20 times per minute on average at the time of hospitalization, disappeared co@ pletely, as a result of which her ability to work usefully increased dramatically, including the ability to use a word proces-sor. Dysuria and insomnia improved and ll””IIPT[’77″fl “FT”” tonic vocalization decreased making words much easier to hear. Thermogra-Fig 5: Superficial electromyography of the trapezium muscle at the time of vocalization phy demonstrated an increase of the skin in a 31 year-old female patient with cerebral palsy of the tension athetosis type. temperature of the hands as well as of the Above:right trapezium muscle and below, left trapezium muscle. Left, before LLLT and right, after LLLT. Decreased electric discharge seen post-LLLT. face and trunk. Electrical discharge from the sternocleidomastold muscle in the sitting position decreased after irradiation, as shown by electromyography. Electrical discharge from the trapezium muscle at the time of vocalization also decreased indicating suppression of involuntary movements and myotonia (Figure 5). The mean duration of 5 vocalizations was clearly prolonged from 4 seconds before irradiation to 7 seconds after 2 weeks of treatment. After mock irradiation using a probe exactly similar to the real probe, that emitted the audible emission indicator but without laser ‘rradiat’on, the duration of vocalization did not change. Fig 6: A 33 year-old male patient with cerebral palsy of the tension athetosis type. (a,b): Before LLLT. Asymmetric posture was seen as well as severe myotonia in the face and the patient could not open his eyes unless he pulled up the upper eyelids with his hands. (cd).- After LLLT. ULT and functional training were given every day for one month. Neck and back pain were ameliorated and eye opening became easier. Symmetric posture was readily taken and motions associated with eating became easier. Case 2: 33 year old male: (Figure 6) The patient was hospitalized for 1 month and was given LLLT and functional training every day. The patient had an asymmetric posture, severe facial myotonia and could not open his eyes unless he pulled up the upper eyelids with his hands. After irradiation, neck and back pain amelio rated, it became easier for him to open his eyes and adopt a more symmetric posture, and movements associated with eating, i.e. mast@ cation and swallowing, also improved and bL-b came more natural. Case 3: 38 year old male (Figure 7): This patient had severe quadriplegia with marked systemic myotonia and had difficulties in lying on his side. After irradiation, systemic otonia was suppressed and assisting the patient became easier. Breathing also i@ proved. Thermography showed an increase of the skin temperature in the face, trunk andFig7: A38year-oldmalepatientwithcerebralpalsyofthetensionathetosistype. upper limbs after 30 minutes of irradiation. (a,b): Before LLLT. The patient had severe quadriplegia with extreme After 60 minutes, the upper limbs which had systemic myotonia and had difficulties in taking the lateral position. (cd): not been observed on the screen before irradia After LLLT. Systemic myotonia was suppressed after first session of LLLT tion were clearly seen after treatment indicating the skin temperature had risen 4 degrees (Figure 8). Discussion Since our first report on LLLT for spastic cere-bral palsy, the usefulness of this therapy has been reported mainly in Japan. In the past, oral administration of a muscle relaxant or a tranquilizer, collar fixation of the neck and traction of the cervical vertebrae were per-formed in an effort to deal with myotonia and pain in tension athetosis, but effective conser- vative modes of treatment for the disease were scarce. Treatment was difficult and not a few cases resulted in cervical spondylosis and cer- vical radiculopathy. We have developed a new therapy wherein the face or neck is irradiated Fig 3: Results of thermography before and after LLLT in a 28 year-old female smoothly with contact laser therapy in the patient with cerebral palsy of the tension athetosis type. (a) Before LLLT. proximal priority method, using the 830 nm (b) 30 minutes after LLLT. (c) 60 minutes after ULT. (d) 90 minutes after LLLT. The rise in systemic skin temperature reached a peak of 4’C after OhLase-3D 1. Myotonia, improvement in con- irradiation and lasted for more than I hour. trol of wide-ranging involuntary movements Fig 8:Results of thermography before and after LLLT in a 38 year-old male patient with cerebral palsy of tension athetosis type. (a) Before ULT. (b) 30 minutes after LLLT. (c) 60 minutes after LLLT. The skin temperature in the face, trunk and upper limbs increased 30 minutes after LLLT. After 60 minutes, the upper limbs which had not been observed before LLLT could be seen and an increase of 4’C in the skin temperature was noted. and improvement of training effect is observed even in adults when LLLT is combined with functional training. The hand-held probe of OhLase-3DI weighs 300g, therefore it is easy to exert adequate pressure on the skin at the target point, and to maintain the slight pressure without the operator’s becoming fatigued. The laser aperture at the tip of the probe cap is fitted with an antireflective window and thus it facilitates smooth irradiation of the body surface. We observed the best effect in comparison to another GaAlAs diode laser with the same output power, but without the probe cap window. In this latter system it was difficult to move the probe smoothly from point to point, and reverse osmosis caused the appearance of small red lumps in the irradiated area when any pressure was applied. In this study, suppression of myotonia lasted for 2 or 3 hours in the face and neck, where myotonia was severe, while it lasted for several days to I week in other regions; moreover, prolongation of the suppressive ef-fect was seen to a certain extent after repeated irradiation. This increased latency effect has been commented on by other researchers, see for example Moore and Calderhead(4) and Ohshiro.(3) As for side effects, asthenia was seen in two patients due to systemic irradiation but this problem was solved by reducing the duration of irradiation or its frequency. In one case in which myotonia was not so marked, it was hard for the patient to hold his head and trunk temporarily due to suppression of myotonia while a temporary slight augmentation of involuntary athe-totic movements was observed after irradiation. Neither the so-called athetose shift, that is an increase of the involuntary movements in regions other than the region where involuntary movement is temporarily suppressed, nor severe side effects, was observed. While there was not a single case in which myotonia was aggravated by LLLT, the patient’s cooperation is im-portant in cases of adult type athetotic cerebral palsy because otherwise it is extremely hard to obtain a therapeutic effect. From our cases, 18 patients out of the original 20 were willing to try further LLLT after their initial session. Conclusions We conducted LLLT in 20 cases of cerebral palsy of the adult tension athetosis type which has been extremely difficult to treat in the past. Improvement of myotonia was observed in 19 patients and amelioration of neck and back pain in the 16 patients who had been suffering from neck and back pain. The duration of sustained effect varied from 1 or 2 hours to a week and it was prolonged by further irradiation sessions. Temporary aggravation of posture maintenance due to suppression of myotonia and asthenia were observed as side effects but no severe side effects were seen. Effect on the autonomic nervous system was suggested as one of the action mechanisms of diode LLLT. LLLT proved very useful in patients with cerebral palsy of the adult tension athetosis type, is easy to apply, is pain-free, is serious side-effect free, and is very well tolerated by patients. References 1:Asagai, Y., Kanai, H., Miura, Y. and Ohshiro, T. (1994): Application of low reactive-level laser therapy (LLLT) in the functional training of cerebral palsy patients. Laser Tberapy, 6: 195-202. 2:Asagai, Y., Inoue, M., Takayasu, R., Aizawa, Y, and Miura, Y. (1 994): Relaxation of spasticity by low energy laser irradiation on cases with cerebral palsy. Kantojournal oforthopedicr and Traumatology, 2 5: 84-90.3:Ohshiro, T (1991): Pain of the neck, shoulders and upper extremities the proximal priority technique. In Ohshiro, T.: “Low Reactive-level Laser Therapy: Practical Introduction.” John Wiley & Sons, Chichester, UK. pp 41-43.4:Moore KC and Calderhead RG (199 1): The clinical appli- cation of low incident power density 830 nm diode laser radiation in the therapy of chronic intractable pain: a historical and optoelectronic rationale and clinical review. International journal of Optoelectronics, 6: 503-520.

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CHARACTERISTICS OF LOW REACTIVE-LEVEL LASER BEAM AND ITS EFFECTS ON THE AUTONOMIC NERVOUS SYSTEM IN PATIENTS WITH CEREBRAL PALSY

Y Asagaii, R Uenol, Y Miura2 and T Ohshiro3

1: Shinano Handicapped Children ‘s Hospital, JJaeano; 2: Department of Orthopaedic Surgery, Tokyo Medical College, Shinjuku, Tokyo; and 3: Japan medical Laser taboratory, Shinanomachi, Tokyo, Japan.

We investigated the characteristics of the low reactive—level laser beam al~l its effects on the autonomic nervous system in patients with cerebral palsy. Subjects and methods: To investigate characteristics of the low reactive-level laser beam, we determined transmissivity in exposed bone specimens and in the human body using a charge coupled device (CCD) camera. Subsequently, we determined changes in the skin temperature of bilateral hands of 50 patients with cerebral palsy. A GaAlAs semiconductor laser was applied to the gohkoku acupuncture point of the left hand, and changes in the skin temperature were determined using a thermotracer TH1106. For other evaluations of the autonomic nervous system, the laser was also applied over the muscles with increased muscle tone all over the body in 12 patients. Thus, the blood flow volume in the common carotid artery was determined by Doppler ultrasonography and high-speed Fourier analysis of the R-R interval in the Holter electrocardiogram was conducted. Results and discussion: The effects of the low reactive—level laser therapy were dispersed throughout the entire body, transmitted possibly via the bone tissues in addition to the blood and Iymphatic fluids. The laser reached a depth of about 3cm at the output level of 100mW. Chronological changes in the skin temperature of the bilateral hands determined by thermography were classified into three types:the flat type, the decreased type, and the increased type. Doppler ultrasOnography revealed an increase in blood flow in the common carotid artery in eight of the 12 patients. Holter electrocardiogrphy also demonstrated increases in the high—frequency components originating from the parasympathetic nerves after irradiation in 8 patients, suggesting the involvement of the autonomic nervous system.

https://www.ncbi.nlm.nih.gov/pubmed/?term=

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LLLT AND MICROCIRCULATION INFLUENCE OF PRELIMINARY LASER IRRADIATION ON STRESS-INDUCED VASCULAR DISORDERS IN THE HEART AND BRAIN

TP Romanova and GE sr

Saratov,Medical University, Saratov, Russia.

Combined pathological stress was modelled in male rats by simultaneous action of immobilization and sound (120 dB, 150-500 Hz) during 2 hours. In animals of the separate group depilated skin area on the femur was irradiated by He-Ne laser (X-632.8 nm, power density-5 mW/cm ) during 15 min immediately before stress. Intact rats served as a control. The stress reaction was established to be accompanied by hyperemia of the heart and the brain tissues. Capillary network density increased as the result of the increase in the number of functioning capillaries in the heart (by 62%, p

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Low Level Laser Therapy (LLLT) For Cerebral Palsy

Kazuaki Tsuchiya, Takashi Harada, Nobuyuki Ushigome, Ikuko Ohkuni, Toshio Ohshiro, Yoshiro Musya, Kazuhiro Mizutani, Yu Maruyama and Toru Suguro

1) Rehabilitation Medicine Toho University2) Orthopaedic Surgery Toho University3) Japan Medical Laser Laboratory4) Department of Orthopaedic Surgery, Ohhashi Hospital, Toho University5) Department of Plastic Surgery, Toho University.

AbstractSpasticity in cerebral palsy (CP) patients is a critical factor preventing voluntary movement, and can also be associated with involuntary clonus. Low reactive-level laser therapy (LLLT) has been reported as having good overall efficacy in CP patients and also in controlling clonus. The present study was designed to evaluate LLLT in the clinical setting to attenuate spasticity in severely handicapped CP patients. We treated 20 CP patients with near infrared (830 nm) LLLT (16.2J/cm2/point, once/week over 10 weeks) as a clinical study at our university hospital and a hospital connected with our university. For spasticity of the hip adductor muscle, the obturator nerve was the target for LLLT, and the tibial nerve was irradiated in the case of triceps surae muscle spasticity. LLLT was indicated for the 10 sessions and the degree of attenuation of spasticity was assessed after the final session. Some degree of efficacy and treatment latency was seen in 14 (70%) of the 20 patients, 5 evaluated as excellent, 6 as very good and 3 as fair. Little or no change was seen in the remaining 6 patients, and in no patient did the symptoms worsen. We concluded that LLLT was an efficacious treatment option in the conservative treatment of CP patients, that it was easilyapplied, non-invasive and pain-free, and that it did not have any adverse side effects.

LASER THERAPY 2008 Vol. 17 (2008) , No. 1 pp.29-33 October

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Effects of Low Level Laser Therapy (LLLT) On Spasticity Caused By Cerebral Vascular Accidents (CVAS)

Nobuyuki Ushigome, Takashi Harada, Ikuko Okuni, Toshio Ohshiro, Yoshiro Musya, Kazuhiro Mizutani, Yu Maruyama, Toru Suguro and Kazuaki Tsuchiya

1) Department of Rehabilitation Medicine, Toho University School of Medicine 2) Japan Medical Laser Laboratory 3) Department of Orthopaedic surgery, Toho University School of Medicine 4) Department of Plastic Surgery, Toho University School of Medicine.

Abstract Spasticity following cerebral vascular accidents (CVAs) is a common occurrence, but remains a problematic entity to treat and interferes with mobility and self-care activities which are critical for successful rehabilitative outcomes. Low reactive-level laser therapy (LLLT) has attracted attention in a number of areas including spasticity associated with cerebral palsy. of the case of post CVA therapy, LLLT has been reported for pain treatment, but not spasticity. the present study examined the efficacy of LLLT in attenuating triceps surae muscle spasticity in CVA patients. the study subjects comprised 15 chronic CVA patients with spasticity, treated at our university hospital between 2002 and 2006. the LLLT device we used was a near infrared (830 nm) semiconductor laser device delivering 1 W in continuous wave (irradiance, 670 mW/cm2) . the laser probe was applied with mild pressure to the skin over the tibial nerve on the affected side, 30 sec/point (dose/point 20.1 J/cm2) repeated 3 times with a 5 sec interval between irradiations. Two sessions were given per week for 1 week. At the end of the week, we recognized LLLT effects in 11 cases out of 15. the other 4 patients had little or no effect but were in their fifties, and had successive bouts of ankle clonus. LLLT is a promising medical treatment for the attenuation of CVA-related spasticity of the triceps surae muscle spasticity, and facilitate voluntary movements in such patients. Further studies are warranted to elucidate the mechanisms by which LLLT can attenuate spasticity.

LASER THERAPY 2008 LASER THERAPY. 2008, Vol. 17, No. 2, p.95-99 November

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Effect of cerebral cortex sulci on near-infrared light propagation during monitoring and treatment

Ting Li, Qingming Luo, and Steven L. Jacques

Oregon Health and Science University, United States Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, China.

Central sulcus substantially affects NIRS/NIRI spatial sensitivity and LLLT fluence rate in the study of light transport within a high-resolution 3D anatomical head structure, allowing deeper penetration of light than previous models predicted.

2012

https://www.researchgate.net/publication/263828521_Effect_of_cerebral_cortex_sulci_on_near-infrared_light_propagation_during_monitoring_and_treatment

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Low-level light therapy of the eye and brain

Julio C Rojas, F Gonzalez-Lima

University of Texas at Austin, 1 University Station A8000, Austin, TX 78712, USA.

Abstract: Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthal- mology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the con- sequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain.

2012

https://www.ncbi.nlm.nih.gov/pubmed/?term=28539775

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