Transcranial Laser Research Articles

Transcranial photobiomodulation therapy improves cognitive test scores in dogs with presumptive canine cognitive dysfunction (CCD): A case series of five dogs

Background: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer’s disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT), or transcranial laser therapy, has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of transcranial photobiomodulation (tPBMT) on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (>9-year-old) dogs with moderate (16-33) to severe (>33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient’s head, 3 times per week for one month and 2 times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30-and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD.

Photobiomodulation in Alzheimer's Disease-A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Alzheimer's disease (AD), as a neurodegenerative disorder, usually develops slowly but gradually worsens. It accounts for approximately 70% of dementia cases worldwide, and is recognized by WHO as a public health priority. Being a multifactorial disease, the origins of AD are not satisfactorily understood. Despite huge medical expenditures and attempts to discover new pharmaceuticals or nanomedicines in recent years, there is no cure for AD and not many successful treatments are available. The current review supports introspection on the latest scientific results from the specialized literature regarding the molecular and cellular mechanisms of brain photobiomodulation, as a complementary method with implications in AD. State-of-the-art pharmaceutical formulations, development of new nanoscale materials, bionanoformulations in current applications and perspectives in AD are highlighted. Another goal of this review was to discover and to speed transition to completely new paradigms for the multi-target management of AD, to facilitate brain remodeling through new therapeutic models and high-tech medical applications with light or lasers in the integrative nanomedicine of the future. In conclusion, new insights from this interdisciplinary approach, including the latest results from photobiomodulation (PBM) applied in human clinical trials, combined with the latest nanoscale drug delivery systems to easily overcome protective brain barriers, could open new avenues to rejuvenate our central nervous system, the most fascinating and complex organ. Picosecond transcranial laser stimulation could be successfully used to cross the blood-brain barrier together with the latest nanotechnologies, nanomedicines and drug delivery systems in AD therapy. Original, smart and targeted multifunctional solutions and new nanodrugs may soon be developed to treat AD.

Transcranial photobiomodulation changes neuronal morphology in the cerebral cortex of rats

Transcranial photobiomodulation improves cerebral cortex metabolism. We hypothesized that chronic laser treatment may stimulate neuronal growth. To test this hypothesis, we investigated the morphology of neurons in the cerebral cortex of rats submitted to brief (2.5 min) daily sham or transcranial laser treatment (810 nm wavelength at 100 mW) for 58 consecutive days. Laser treatment increased the number of dendritic nodes and ends, and reduced the total dendritic length in neurons of the cerebral cortex. Taken together, our data indicate that chronic transcranial photobiomodulation induces morphological neuroplasticity in the cerebral cortex of rats.

Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains

In cellular bioenergetics, cytochrome c oxidase (CCO) is the enzyme responsible for oxygen consumption in the mitochondrial electron transport chain, which drives oxidative phosphorylation for adenosine triphosphate (ATP) production. CCO is also the major intracellular acceptor of photons in the light wavelengths used for photobiomodulation (PBM). Brain function is critically dependent on oxygen consumption by CCO for ATP production. Therefore, our objectives were (1) to conduct the first detailed brain mapping study of the effects of PBM on regional CCO activity, and (2) to compare the chronic effects of PBM on young and aged brains. Specifically, we used quantitative CCO histochemistry to map the differences in CCO activity of brain regions in healthy young (4 months old) and aged (20 months old) rats from control groups with sham stimulation and from treated groups with 58 consecutive days of transcranial laser PBM (810 nm wavelength and 100 mW power). We found that aging predominantly decreased regional brain CCO activity and systems-level functional connectivity, while the chronic laser stimulation predominantly reversed these age-related effects. We concluded that chronic PBM modified the effects of aging by causing the CCO activity on brain regions in laser-treated aged rats to reach levels similar to those found in young rats. Given the crucial role of CCO in bioenergetics, PBM may be used to augment brain and behavioral functions of older individuals by improving oxidative energy metabolism.

Reversal of Acquired Prosopagnosia Using Quantitative Electroencephalography-Guided Laser Therapy.

Background: Currently treatment for prosopagnosia is limited. Methods: We report the reversal of acquired associative-type prosopagnosia (AAP) using quantitative electroencephalography (qEEG)-guided transcranial laser therapy (qGLT) in a subject with temporal lobe epilepsy (TLE) and mild cognitive impairment (MCI). Results: Objective and subjective measures of improvement in AAP, TLE, and MCI are presented. Additional improvement, measured through qEEG, was found 1-month post-treatment. Conclusions: There was no recurrence of AAP for 1 year. We conclude that further research into the utility of qGLT in the treatment of AAP is warranted.

Transcranial photobiomodulation (laser) therapy for cognitive impairment: A review of molecular mechanisms and potential application to canine cognitive dysfunction (CCD).

Alzheimer’s disease (AD) is a common degenerative brain disorder of aging people which shares many clinical and pathological features with canine cognitive dysfunction (CCD). CCD is considered a naturally occurring model of human AD. Transcranial photobiomodulation therapy (tPBMT), also known as transcranial laser therapy, entails delivering photons of near infrared to infrared light from the skin surface of the scalp to the underlying brain. Specific molecular cellular receptors, called chromophores, absorb this energy, and use it to initiate biological reactions with potential therapeutic benefit. Improvement in cognitive ability using tPBMT has been documented in rodent AD models and human clinical trials. The purposes of this review are to provide an overview of the suspected molecular mechanisms of action of tPBMT for the treatment of cognitive decline and to propose potential application of this treatment modality for dogs affected by CCD.

Transcranial Laser Therapy Does Not Improve Cognitive and Post-Traumatic Stress Disorder-Related Behavioral Traits in Rats Exposed to Repetitive Low-Level Blast Injury.

Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Transcranial laser therapy (TLT) uses low-power lasers emitting light in the far- to near-infrared ranges. Beneficial effects of TLT have been reported in neurological and mental-health–related disorders in humans and animal models, including TBI. Rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits. We tested whether TLT treatment could reverse these traits. Rats received a 74.5-kPa blast or sham exposures delivered one per day for 3 consecutive days. Beginning at 34 weeks after blast exposure, the following groups of rats were treated with active or sham TLT: 1) Sham-exposed rats (n = 12) were treated with sham TLT; 2) blast-exposed rats (n = 13) were treated with sham TLT; and 3) blast-exposed rats (n = 14) were treated with active TLT. Rats received 5 min of TLT five times per week for 6 weeks (wavelength, 808 nm; power of irradiance, 240 mW). At the end of treatment, rats were tested in tasks found previously to be most informative (novel object recognition, novel object localization, contextual/cued fear conditioning, elevated zero maze, and light/dark emergence). TLT did not improve blast-related effects in any of these tests, and blast-exposed rats were worse after TLT in some anxiety-related measures. Based on these findings, TLT does not appear to be a promising treatment for the chronic cognitive and mental health problems that follow blast injury.

Photobiomodulation Improves the Inflammatory Response and Intracellular Signaling Proteins Linked to Vascular Function and Cell Survival in the Brain of Aged Rats.

Photobiomodulation is a non-pharmacological tool widely used to reduce inflammation in many tissues. However, little is known about its effects on the inflammatory response in the aged brain. We conducted the study to examine anti-inflammatory effects of photobiomodulation in aging brains. We used aged rats (20months old) with control (handled, laser off) or transcranial laser (660nm wavelength, 100 mW power) treatments for 10 consecutive days and evaluated the level of inflammatory cytokines and chemokines, and the expression and activation of intracellular signaling proteins in the cerebral cortex and the hippocampus. Inflammatory analysis showed that aged rats submitted to transcranial laser treatment had increased levels of IL-1alpha and decreased levels of IL-5 in the cerebral cortex. In the hippocampus, the laser treatment increased the levels of IL-1alpha and decreased levels of IL-5, IL-18, and fractalkine. Regarding the intracellular signaling proteins, a reduction in the ERK and p38 expression and an increase in the STAT3 and ERK activation were observed in the cerebral cortex of aged rats from the laser group. In addition, the laser treatment increased the hippocampal expression of p70S6K, STAT3, and p38 of aged rats. Taken together, our data indicate that transcranial photobiomodulation can improve the inflammatory response and the activation of intracellular signaling proteins linked to vascular function and cell survival in the aged brain.

5.5 TRANSCRANIAL PHOTOBIOMODULATION IN THE TREATMENT OF SOCIAL AND EXECUTIVE FUNCTION DEFICITS IN AUTISM SPECTRUM DISORDER

No established treatments exist for the core features of autism spectrum disorder (ASD). Transcranial photobiomodulation (tPBM) is thought to enhance neuronal activity and promote cellular plasticity. Recent clinical research interest has focused on its role as a potential treatment in mental illness and neurological conditions including depression and traumatic brain injury. The efficacy of tPBM treatment in ASD remains unexplored. Adult participants meeting the diagnostic criteria for ASD were enrolled to receive twice-weekly tPBM treatments for 8 weeks in an open-label single-group design. ASD symptom severity and executive function deficits were assessed at baseline and endpoint by clinician-, self-, and informant-rated measures. Paired samples t test analyses were performed. Findings were placed in the context of the existing sparse research consisting of clinical trials identified by a detailed MEDLINE literature search with resulting articles assessed for strength of evidence. Finally, interim results from the ongoing 8-week open-label study of daily tPBM treatment in youth with ASD diagnosis are presented. Ten participants (9 males; 30.0 ± 11.9 years old) completed the study. Five participants (50%) met the responder criteria at endpoint. Eight-week transcranial laser therapy (TLT) was associated with significant improvement in ASD severity (Total SRS-2 reduction: –30.6 ± 23, p < 0.001), particularly in Social Awareness (–3.0 ± 1.9, p < 0.001), Social Communication (–10.3 ± 6, p < 0.001), Social Motivation (–5.0 ± 2.4, p < 0.001), and Restricted/Repetitive Behaviors (–7.4 ± 4.1, p < 0.001). Statistically significant improvement at endpoint was shown in Global Assessment of Functioning (GAF) scores (+12.8 ± 4.2, p < 0.001) and Quality of Life Enjoyment and Satisfaction Questionnaire scores (+6.0 ± 7.9, p = 0.02). There were no treatment-limiting adverse events. The adherence rate was 98%. tPBM treatment was associated with improvements in the core features of ASD as well as executive dysfunction, and a significant improvement in overall function. The 98% rate of adherence to scheduled study visits and procedures suggests a high potential of acceptance of this noninvasive intervention. tPBM is a safe, feasible treatment approach and further research into its efficacy in the treatment of the core features of ASD is warranted.

Transcranial Laser Photobiomodulation Improves Intracellular Signaling Linked to Cell Survival, Memory and Glucose Metabolism in the Aged Brain: A Preliminary Study.

Aging is often accompanied by exacerbated activation of cell death-related signaling pathways and decreased energy metabolism. We hypothesized that transcranial near-infrared laser may increase intracellular signaling pathways beneficial to aging brains, such as those that regulate brain cell proliferation, apoptosis, and energy metabolism. To test this hypothesis, we investigated the expression and activation of intracellular signaling proteins in the cerebral cortex and hippocampus of aged rats (20 months old) treated with the transcranial near-infrared laser for 58 consecutive days. As compared to sham controls, transcranial laser treatment increased intracellular signaling proteins related to cell proliferation and cell survival, such as signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB), also known as Akt that is linked to glucose metabolism. In addition, ERK is linked to memory, while ERK and JNK signaling pathways regulate glucose metabolism. Specifically, the laser treatment caused the activation of STAT3, ERK, and JNK signaling proteins in the cerebral cortex. In the hippocampus, the laser treatment increased the expression of p70S6K and STAT3 and the activation of Akt. Taken together, the data support the hypothesis that transcranial laser photobiomodulation improves intracellular signaling pathways linked to cell survival, memory, and glucose metabolism in the brain of aged rats.

Improved Spatial Memory And Neuroinflammatory Profile Changes in Aged Rats Submitted to Photobiomodulation Therapy.

Recent evidences have shown the therapeutic potential of transcranial photobiomodulation on traumatic brain injury and Alzheimer's disease. Despite the promising benefits in the brain, little is known about the laser's effects in the absence of pathological conditions. We submitted young (4months old) and aged (20months old) rats to transcranial low-level laser and evaluated their exploratory activity and habituation in open field, anxiety in elevated plus maze, spatial memory in Barnes maze, and aversive memory in a step-down inhibitory avoidance task. Additionally, the levels of a panel of inflammatory cytokines and chemokines were quantified in two different brain regions: the cerebral cortex and the hippocampus. Young and aged rats submitted to transcranial laser exhibited better cognitive performance in Barnes maze than did control rats. Transcranial laser therapy decreased cortical levels of GM-CSF, IL-10, MCP-1, LIX, and TNFα in young rats and IL-5 in aged rats. High levels of IL-6, IL-10, and TNF-alpha were found in the cerebral cortex of aged rats submitted to transcranial laser. In the hippocampus, a decrease in IP-10 and fractalkine levels was observed in the aged rats from the laser group when compared to the aged rats from the control group. Our data indicate that transcranial photobiomodulation improves spatial learning and memory and alters the neuroinflammatory profile of young and aged rats' brains.

Transcranial laser stimulation: Mitochondrial and cerebrovascular effects in younger and older healthy adults

BackgroundTranscranial laser stimulation is a novel method of noninvasive brain stimulation found safe and effective for improving prefrontal cortex neurocognitive functions in healthy young adults. This method is different from electric and magnetic stimulation because it causes the photonic oxidation of cytochrome-c-oxidase, the rate-limiting enzyme for oxygen consumption and the major intracellular acceptor of photons from near-infrared light. This photobiomodulation effect promotes mitochondrial respiration, cerebrovascular oxygenation and neurocognitive function. Pilot studies suggest that transcranial photobiomodulation may also induce beneficial effects in aging individuals. ObjectivesRandomized, sham-controlled study to test photobiomodulation effects caused by laser stimulation on cytochrome-c-oxidase oxidation and hemoglobin oxygenation in the prefrontal cortex of 68 healthy younger and older adults, ages 18–85. MethodsBroadband near-infrared spectroscopy was used for the noninvasive quantification of bilateral cortical changes in oxidized cytochrome-c-oxidase and hemoglobin oxygenation before, during and after 1064-nm wavelength laser (IR-A laser, area: 13.6 cm2, power density: 250 mW/cm2) or sham stimulation of the right anterior prefrontal cortex (Brodmann Area 10). ResultsAs compared to sham control, there was a significant laser-induced increase in oxidized cytochrome-c-oxidase during laser stimulation, followed by a significant post-stimulation increase in oxygenated hemoglobin and a decrease in deoxygenated hemoglobin. Furthermore, there was a greater laser-induced effect on cytochrome-c-oxidase with increasing age, while laser-induced effects on cerebral hemodynamics decreased with increasing age. No adverse laser effects were found. ConclusionThe findings support the use of transcranial photobiomodulation for cerebral oxygenation and alleviation of age-related decline in mitochondrial respiration. They justify further research on its therapeutic potential in neurologic and psychiatric diseases.

Efficacy of Transcranial Near-Infrared Light Treatment in ASD: Update on Open-Label Proof of Concept Study of a Novel Approach

ASD is characterized by variable presentation of difficulties with socialization, communication, and restrictive/repetitive behaviors (RRBs), for which no established pharmacological treatment exists. Transcranial laser emitting diode (LED) therapy (TLT) is a noninvasive intervention with near-infrared light to the forebrain. It is absorbed by cytochrome c oxidase in mitochondria and increases energy metabolism, leading to cellular plasticity and cytoprotection. Recently, TLT was found to be safe and effective in the treatment of depression.

Photobiomodulation and Coenzyme Q10 Treatments Attenuate Cognitive Impairment Associated With Model of Transient Global Brain Ischemia in Artificially Aged Mice.

Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10) administration are known to stimulate mitochondrial electron transport that potentially may reverse the effects of cerebral ischemia in aged animals. We tested the hypothesis that the effects of PBM and CoQ10, separately or in combination, improve cognition in a mouse model of transient cerebral ischemia superimposed on a model of aging. We modeled aging by 6-week administration of D-galactose (500 mg/kg subcutaneous) to mice. We subsequently induced transient cerebral ischemia by bilateral occlusion of the common carotid artery (BCCAO). We treated the mice with PBM (810 nm transcranial laser) or CoQ10 (500 mg/kg by gavage), or both, for 2 weeks after surgery. We assessed cognitive function by the Barnes and Lashley III mazes and the What-Where-Which (WWWhich) task. PBM or CoQ10, and both, improved spatial and episodic memory in the mice. Separately and together, the treatments lowered reactive oxygen species and raised ATP and general mitochondrial activity as well as biomarkers of mitochondrial biogenesis, including SIRT1, PGC-1α, NRF1, and TFAM. Neuroinflammatory responsiveness declined, as indicated by decreased iNOS, TNF-α, and IL-1β levels with the PBM and CoQ10 treatments. Collectively, the findings of this preclinical study imply that the procognitive effects of NIR PBM and CoQ10 treatments, separately or in combination, are beneficial in a model of transient global brain ischemia superimposed on a model of aging in mice.

Transcranial Laser Therapy of Post-Traumatic stress disorder in an Autistic Patient

Transcranial Laser Therapy of Post-Traumatic stress disorder in an Autistic Patient

Влияние транскраниального лазерного воздействия на условно-рефлекторную деятельность крыс

Влияние транскраниального лазерного воздействия на условно-рефлекторную деятельность крыс

Low-level laser therapy modulates demyelination in mice

There are no effective therapies for remyelination. Low-level laser therapy (LLLT) has been found advantageous in neurogenesis promotion, cell death prevention, and modulation of inflammation in central and peripheral nervous system models. The purpose of this study was to analyse LLLT effects on cuprizone-induced demyelination. Mice were randomly distributed into three groups: Control Laser (CTL), Cuprizone (CPZ), and Cuprizone Laser (CPZL). Mice from CPZ and CPZL groups were exposed to a 0.2% cuprizone oral diet for four complete weeks. Six sessions of transcranial laser irradiation were applied on three consecutive days, during the third and fourth weeks, with parameters of 36 J/cm2, 50 mW, 0.028 cm2 spot area, continuous wave, 1 J, 20 s, 1.78 W/cm2 in a single point equidistant between the eyes and ears of CTL and CPZL mice. Motor coordination was assessed by the rotarod test. Twenty-four hours after the last laser session, all animals were euthanized, and brains were extracted. Serum was obtained for lactate dehydrogenase toxicity testing. Histomorphological analyses consisted of Luxol Fast Blue staining and immunohistochemistry. The results showed that laser-treated animals presented motor performance improvement, attenuation of demyelination, increased number of oligodendrocyte precursor cells, modulated microglial and astrocytes activation, and a milder toxicity by cuprizone. Although further studies are required, it is suggested that LLLT represents a feasible therapy for demyelinating diseases.

5.20 Efficacy of Transcranial Near-Infrared Light Treatment in ASD: Interim Analysis of an Open-Label Proof of Concept Study of a Novel Approach

ASD is characterized by variable presentation of difficulties with socialization, communication, and restrictive/repetitive behaviors (RRB), for which no established pharmacological treatment exists. Transcranial Laser Emitting Diode (LED) Therapy (TLT) is a noninvasive intervention with near-infrared light to forebrain. It is absorbed by cytochrome c oxidase in mitochondria and increases energy metabolism, leading to cellular plasticity and cytoprotection. Recently, TLT was found to be safe and effective in the treatment of depression. Effects of TLT on ASD symptoms remains to be explored.

Effect of Transcranial Laser on Somatosensory Integration in Patients with Nonspecific Neck Pain: Randomized Controlled Trial

Effect of Transcranial Laser on Somatosensory Integration in Patients with Nonspecific Neck Pain: Randomized Controlled Trial

Treating cognitive impairment with transcranial low level laser therapy

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.