Three-dimensional irradiance and temperature distributions resulting from transdermal application of laser light to human knee-A numerical approach.

The use of light for therapeutic applications requires light-absorption by cellular chromophores at the target tissues and the subsequent photobiomodulation (PBM) of cellular biochemical processes. For transdermal deep tissue light therapy (tDTLT) to be clinically effective, a sufficiently large number of photons must reach and be absorbed at the targeted deep tissue sites. Thus, delivering safe and effective tDTLT requires understanding the physics of light propagation in tissue. This study simulates laser light propagation in an anatomically accurate human knee model to assess the light transmittance and light absorption-driven thermal changes for eight commonly used laser therapy wavelengths (600-1200 nm) at multiple skin-applied irradiances (W cm-2 ) with continuous wave (CW) exposures. It shows that of the simulated parameters, 2.38 W cm-2 (30 W, 20 mm beam radius) of 1064 nm light generated the least tissue heating -4°C at skin surface, after 30 s of CW irradiation, and the highest overall transmission-approximately 3%, to the innermost muscle tissue.

Pilot Study on Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Electrical Oscillations: A Potential Therapeutic Target in Alzheimer's Disease.

BACKGROUND: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. OBJECTIVE: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). METHODS: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2; 65.8 J/cm2; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2; 33%; 21.7 J/cm2; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. RESULTS: c-tPBM significantly boosted gamma (t = 3.02, df = 7, p < 0.02) and beta (t = 2.91, df = 7, p < 0.03) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < 0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. CONCLUSION: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR.

Retrospective Observational Study and Analysis of Two Different Photobiomodulation Therapy Protocols Combined with Rehabilitation Therapy as Therapeutic Interventions for Canine Degenerative Myelopathy.

Objective: The objective of this retrospective review was to examine the impact that adding photobiomodulation therapy (PBMt) to rehabilitation therapy had on the pathology of degenerative myelopathy (DM) in canine patients. Background: Canine DM is a progressive, fatal neurodegenerative disease for which there exists a dearth of effective treatments, limiting clinicians to pursue symptom palliation. Methods: Clinical records of dogs referred for presumed DM to a specialty rehabilitation facility were screened for patients meeting study criteria. Qualifying patients were divided into two groups: Protocol A (PTCL-A) and Protocol B (PTCL-B) group, based on the PBMt protocol used. Data related to demographics, diagnostics, rehabilitation protocols, and progression of clinical signs were collected. Data were analyzed to determine differences in outcomes between the two treated groups and historical data expectations, as given by a previously published study. Results: The times between symptom onset and euthanasia of dogs in the PTCL-B group: 38.2 ± 14.67 months (mean ± SD), were significantly longer than those of dogs in the PTCL-A group: 11.09 ± 2.68 months. Similarly, the times between symptom onset and nonambulatory paresis (NAP) or paralysis of dogs in the PTCL-B group: 31.76 ± 12.53 months, were significantly longer than those of dogs in the PTCL-A group: 8.79 ± 1.60 months. Further, Kaplan-Meier survival analysis showed that the times from symptom onset to NAP of dogs in the PTCL-B group were significantly longer than those of dogs in the PTCL-A group (Mantel-Cox Log Rank statistic = 20.434, p < 0.05) or the historical data group (Mantel-Cox Log Rank statistic = 16.334, p < 0.05). Conclusions: The data reviewed show significantly slower disease progression-longer survival times-for patients in the PTCL-B group than those in the PTCL-A group or published historical data. Further studies are warranted.

Penetration Profiles of Visible and Near-Infrared Lasers and Light-Emitting Diode Light Through the Head Tissues in Animal and Human Species: A Review of Literature.

Background and objective: Photobiomodulation (PBM) therapy is a promising and noninvasive approach to stimulate neuronal function and improve brain repair. The optimization of PBM parameters is important to maximize effectiveness and tolerability. Several studies have reported on the penetration of visible-to-near-infrared (NIR) light through various animal and human tissues. Scientific findings on the penetration of PBM light vary, likely due to use of different irradiation parameters and to different characteristics of the subject such as species, age, and gender. Materials and methods: In this article, we review published data on PBM penetration through the tissues of the head in both animal and human species. The patterns of visible-to-NIR light penetration are summarized based on the following study specifications: wavelength, coherence, operation mode, beam type and size, irradiation site, species, age, and gender. Results: The average penetration of transcranial red/NIR (630-810 nm) light ranged 60-70% in C57BL/6 mouse (skull), 1-10% in BALB/c mouse (skull), 10-40% in Sprague-Dawley rats (scalp plus skull), 20% in Oryctolagus cuniculus rabbit (skull), 0.11% in pig (scalp plus skull), and 0.2-10% in humans (scalp plus skull). The observed variation in the reported values is due to the difference in factors (e.g., wavelengths, light coherence, tissue thickness, and anatomic irradiation site) used by researchers. It seems that these data challenge the applicability of the animal model data on transcranial PBM to humans. Nevertheless, two animal models seem particularly promising, as they approximate penetration in humans: (I) Penetration of 808 nm laser through the scalp plus skull was 0.11% in the pig head; (II) Penetration of 810 nm laser through intact skull was 1.75% in BALB/c mouse. Conclusions: In conclusion, it is worthwhile mentioning that since the effectiveness of brain PBM is closely dependent on the amount of light energy reaching the target neurons, further quantitative estimation of light penetration depth should be performed to validate the current findings.

Effect of deep tissue laser therapy treatment on peripheral neuropathic pain in older adults with type 2 diabetes: a pilot randomized clinical trial.

BACKGROUND: This study assessed the safety and efficacy of deep tissue laser therapy on the management of pain, functionality, systemic inflammation, and overall quality of life of older adults with painful diabetic peripheral neuropathy. METHODS: The effects of deep tissue laser therapy (DTLT) were assessed in a randomized, double-masked, sham-controlled, interventional trial. Forty participants were randomized (1:1) to receive either DTLT or sham laser therapy (SLT). In addition to the standard-of-care treatment, participants received either DTLT or SLT twice weekly for 4 weeks and then once weekly for 8 weeks (a 12-week intervention period). The two treatments were identical, except that laser emission was disabled during SLT. Assessments for pain, functionality, serum levels of inflammatory biomarkers, and quality of life (QOL) were performed at baseline and after the 12-week intervention period. The results from the two treatments were compared using ANOVA in a pre-test-post-test design. RESULTS: All participants randomized to the DTLT group and 85% (17 of 20) of participants randomized to the SLT group completed the trial. No significant differences in baseline characteristics between the groups were observed. After the 12-week intervention period, pain levels significantly decreased in both groups and were significantly lower in the DTLT group than in the SLT group. The Timed Up and Go test times (assessing functionality) were significantly improved in both groups and were 16% shorter in the DTLT group than in the SLT group. Serum levels of IL-6 decreased significantly in both groups. Additionally, serum levels of MCP-1 decreased significantly in the DTLT group but not in the SLT group. Patients' quality of life improved significantly in the DTLT group but not in the SLT group. CONCLUSIONS: Deep tissue laser therapy significantly reduced pain and improved the quality of life of older patients with painful diabetic peripheral neuropathy. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008739 . [Registered on: 02/06/2017]. The trial was registered retrospectively.

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.

Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. Materials and methods: We conducted a double-blind, sham-controlled study on the safety and efficacy [change in Hamilton Depression Rating Scale (HAM-D17) total score at end-point] of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. Results: The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.

Flexible nine-channel photodetector probe facilitated intraspinal multisite transcutaneous photobiomodulation therapy dosimetry in cadaver dogs.

Noninvasive photobiomodulation therapy (PBMT) of spinal cord disease remains speculative due to the lack of evidence for whether photobiomodulatory irradiances can be transcutaneously delivered to the spinal cord under a clinically acceptable PBMT surface irradiation protocol. We developed a flexible nine-channel photodetection probe for deployment within the spinal canal of a cadaver dog after hemilaminectomy to measure transcutaneously transmitted PBMT irradiance at nine sites over an eight-cm spinal canal length. The probe was built upon a 6.325-mm tubular stem, to the surface of which nine photodiodes were epoxied at approximately 1 cm apart. The photodiode has a form factor of 4.80 mm×2.10 mm×1.15 mm (length×width×height). Each photodiode was individually calibrated to deliver 1 V per 7.58 µW/cm2 continuous irradiance at 850 nm. The outputs of eight photodiodes were logged concurrently using a data acquisition module interfacing eight channels of differential analog signals, while the output of the ninth photodiode was measured by a precision multimeter. This flexible probe rendered simultaneous intraspinal (nine-site) measurements of transcutaneous PBMT irradiations at 980 nm in a pilot cadaver dog model. At a surface continuous irradiance of 3.14 W/cm2 applied off-contact between L1 and L2, intraspinal irradiances picked up by nine photodiodes had a maximum of 327.48 µW/cm2 without the skin and 5.68 µW/cm2 with the skin.

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

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.

Pulsed light irradiation improves behavioral outcome in a rat model of chronic mild stress.

BACKGROUND AND OBJECTIVE: Transcranial laser therapy (TLT) has been used successfully for the treatment of stroke in animal models and clinical trials. These results support the hypothesis that TLT could be used to treat other central nervous system conditions, such as depression. Current therapy for depression emphasizes pharmaco-therapeutics. However, these interventions often cause unwanted side effects. Here, TLT as a treatment for depression was studied in a rat model of chronic mild stress (CMS). STUDY DESIGN/MATERIAL AND METHODS: Wistar rats were randomized into four experimental groups (n = 8): (1) No-stress; (2) stress without treatment (Stress); (3) stress treated with an antidepressant (Drug); and (4) stress treated with TLT (TLT). The rats in the stress groups were exposed sequentially to a variety of mild stressors for 8 weeks. Rats were weighed weekly. After 5 weeks of stressing, the Drug group received a daily injection of fluoxetine (10 mg/kg), and the TLT group was irradiated transcranially 3 times a week (810 nm wavelength laser, 3 mm diameter probe, 350 mW peak power, 100 Hz with 20% duty cycle, 2-minute treatment time, 120 J/cm(2) average energy density on skin surface). After 3 weeks of treatment, a forced swimming test (FST) was performed and recorded for behavioral assessment. Animals were euthanized after 8 weeks of the study. RESULTS: The No-stress group had significantly higher body weight than stress groups from week 5 (P < 0.05). No weight difference was found between the stress groups before treatment. However, the Drug group had significantly less body weight than both Stress and TLT groups after 2 weeks of treatment (P < 0.05). FST showed that the Stress group had significantly more immobility than the No-stress group (P < 0.05). Both Drug and TLT groups had significantly less immobility than the stress group (P < 0.05). There was no significant difference in immobility between both Drug and TLT groups (P = 0.62). CONCLUSIONS: TLT was comparable to fluoxetine in improving the behavioral outcome after CMS. TLT did not cause weight loss, which is consistently seen in patients treated with fluoxetine. This study demonstrates that TLT has potential as an effective treatment for depression.

Dose response effects of 810 nm laser light on mouse primary cortical neurons.

BACKGROUND AND OBJECTIVES: In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from embryonic mouse brains. STUDY DESIGN/MATERIALS AND METHODS: Neurons were irradiated with fluences of 0.03, 0.3, 3, 10, or 30 J/cm(2) of 810-nm laser delivered over varying times at 25 mW/cm(2) and intracellular levels of reactive oxygen species (ROS), nitric oxide and calcium were measured using fluorescent probes within 5 minutes of the end of irradiation. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). RESULTS: Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluences. ROS was significantly induced at low fluences, followed by a decrease and a second larger increase at 30 J/cm(2). Nitric oxide levels showed a similar pattern of a double peak but values were less significant compared to ROS. CONCLUSIONS: The results suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling processes which in turn may be responsible for the beneficial stimulatory effects of the low level laser. At higher fluences beneficial mediators are reduced and high levels of Janus-type mediators such as ROS and NO (beneficial at low concentrations and harmful at high concentrations) may be responsible for the damaging effects of high-fluence light and the overall biphasic dose response.

Transcranial laser therapy attenuates amyloid-ß peptide neuropathology in amyloid-ß protein precursor transgenic mice.

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-ß protein precursor (AßPP) 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-ß (Aß) levels, plasma Aß levels, cerebrospinal fluid Aß levels, soluble AßPP (sAßPP) levels, and behavioral changes. The numbers of Aß 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 AßPP transgenic mice. All TLT doses produced an increase in sAßPPα and a decrease in CTFß levels consistent with inhibition of the ß-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.

Long-term safety of single and multiple infrared transcranial laser treatments in Sprague-Dawley rats.

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.

Effect of pulsing in low-level light therapy.

BACKGROUND AND OBJECTIVE: Low level light (or laser) therapy (LLLT) is a rapidly growing modality used in physical therapy, chiropractic, sports medicine and increasingly in mainstream medicine. LLLT is used to increase wound healing and tissue regeneration, to relieve pain and inflammation, to prevent tissue death, to mitigate degeneration in many neurological indications. While some agreement has emerged on the best wavelengths of light and a range of acceptable dosages to be used (irradiance and fluence), there is no agreement on whether continuous wave or pulsed light is best and on what factors govern the pulse parameters to be chosen. STUDY DESIGN/MATERIALS AND METHODS: The published peer-reviewed literature was reviewed between 1970 and 2010. RESULTS: The basic molecular and cellular mechanisms of LLLT are discussed. The type of pulsed light sources available and the parameters that govern their pulse structure are outlined. Studies that have compared continuous wave and pulsed light in both animals and patients are reviewed. Frequencies used in other pulsed modalities used in physical therapy and biomedicine are compared to those used in LLLT. CONCLUSION: There is some evidence that pulsed light does have effects that are different from those of continuous wave light. However further work is needed to define these effects for different disease conditions and pulse structures.

Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5'-triphosphate (ATP) content following embolic strokes in rabbits.

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 naïve 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.

Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy.

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.

low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits.

Low-level laser therapy (LLLT) has been evaluated in this study as a potential therapy for traumatic brain injury (TBI). LLLT has been found to modulate various biological processes. Following TBI in mice, we assessed the hypothesis that LLLT might have a beneficial effect on their neurobehavioral and histological outcome. TBI was induced by a weight-drop device, and motor function was assessed 1 h post-trauma using a neurological severity score (NSS). Mice were then divided into three groups of eight mice each: one control group that received a sham LLLT procedure and was not irradiated; and two groups that received LLLT at two different doses (10 and 20 mW/cm(2) ) transcranially. An 808-nm Ga-As diode laser was employed transcranially 4 h post-trauma to illuminate the entire cortex of the brain. Motor function was assessed up to 4 weeks, and lesion volume was measured. There were no significant changes in NSS at 24 and 48 h between the laser-treated and non-treated mice. Yet, from 5 days and up to 28 days, the NSS of the laser-treated mice were significantly lower (p < 0.05) than the traumatized control mice that were not treated with the laser. The lesion volume of the laser treated mice was significantly lower (1.4%) than the non-treated group (12.1%). Our data suggest that a non-invasive transcranial application of LLLT given 4 h following TBI provides a significant long-term functional neurological benefit. Further confirmatory trials are warranted.