Transcranial photobiomodulation for brain diseases: review of animal and human studies including mechanisms and emerging trends.

The brain diseases account for 30% of all known diseases. Pharmacological treatment is hampered by the blood-brain barrier, limiting drug delivery to the central nervous system (CNS). Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability. tPBM has been widely used in pre-clinical experiments and clinical trials for treating brain diseases, such as stroke and Alzheimer's disease. This review provides a comprehensive overview of tPBM. We summarize emerging trends and new discoveries in tPBM based on over one hundred references published in the past 20 years. We discuss the advantages and disadvantages of tPBM and highlight successful experimental and clinical protocols for treating various brain diseases. A better understanding of tPBM mechanisms, the development of guidelines for clinical practice, and the study of dose-dependent and personal effects hold great promise for progress in treating brain diseases.

Effect of energy level of photobiomodulation therapy on bone repair in rats / Efecto del nivel de energía de la terapia de fotobiomodulación sobre la reparación ósea en ratas

Abstract The aim of this experimental study was to determine the effect of photobiomodulation therapy on bone repair in a rat tibia osteotomy model at 15 and 30 days. The sample consisted of 36 male Holtzman rats that were randomized into 6 equal groups. Groups A1 and A2: osteotomy + 1 J laser energy. Groups B1 and B2: osteotomy + 3 J laser energy. Groups C1 and C2 (controls): osteotomy only. The bone repair was analyzed by histological evaluation of osteoblasts and osteocytes both at 15 days (groups A1, B1, and C1) and at 30 days (groups A2, B2, and C2). Within the results, in all groups a greater number of osteoblasts was found at 15 days vs 30 days (p<0.05), and a greater number of osteocytes in B1 and C2 vs B2 and C1, respectively (p<0.05). When evaluating the 3 groups worked up to 15 days, more osteoblasts were found in A1 and C1 vs B1 (p<0.001); and osteocytes predominated in A1 and B1 vs C1 (p<0.001). At 30 days there was a greater quantity of osteoblasts in C2 vs A2 and B2 (p<0.05) and of osteocytes in C2 vs B2 (p<0.05). It is concluded that 1 J photobiomodulation therapy improved bone repair at 15 days; however, this improvement was not observed at 30 days because there were no differences between the irradiated groups and the control.

Resumen El objetivo de este estudio experimental fue determinar el efecto de terapia de fotobiomodulación sobre la reparación ósea en un modelo de osteotomía de tibia de rata a los 15 y 30 días. La muestra estuvo compuesta por 36 ratas Holtzman macho que se aleatorizaron en 6 grupos iguales. Grupos A1 y A2: osteotomía + energía láser de 1 Joule. Grupos B1 y B2: osteotomía + energía láser 3 Joule. Grupos C1 y C2 (controles): solo osteotomía. La reparación ósea fue analizada por evaluación histológica de osteoblastos y osteocitos tanto a los 15 días (grupos A1, B1 y C1) como a los 30 días (grupos A2, B2 y C2). Como resultados se encontró que en todos los grupos hubo mayor número de osteoblastos a los 15 días vs. 30 días (p<0,05), y mayor número de osteocitos en B1 y C2 vs B2 y C1, respectivamente (p<0,05). Al evaluar a los animales a los 15 días, se observó mayor número de osteoblastos en A1 y C1 vs B1 (p<0.001); y mayor número de osteocitos en A1 y B1 vs C1 (p<0,001). Al evaluar a los ratones a los 30 días hubo mayor cantidad de osteoblastos en C2 vs A2 y B2 (p<0,05) y de osteocitos en C2 vs B2 (p<0,05). Se concluye que la terapia de fotobiomodulación con 1 Joule mejoró la reparación ósea a los 15 días; sin embargo, dicha mejora no se observó a los 30 días porque no hubo diferencias entre los grupos irradiados y el control.

Reverse skin aging signs by red light photobiomodulation.

BACKGROUND: Photobiomodulation is a process by which the absorption of red light energy produces a series of physiological effects at the cellular level such as the enhancement of mitochondrial Adenosine Triphosphate (ATP) production, cell signaling and growth factor synthesis, and the reduction of oxidative stress. Light emitting diodes (LEDs) photobiomodulation is an increasingly popular therapy for treating skin problems, especially for reversing the signs of skin aging. OBJECTIVE: The objective of this study is to demonstrate the effectiveness of a photobiomodulation treatment using red LEDs on the facial skin at a rate of two sessions per week for 3 months. The LED mask used is the Skin Light Dior x Lucibel mask diffusing a cold red light with a wavelength of 630 ± 10 nm and a power of 15.6 J/cm2 for a duration of 12 min. METHOD: In order to demonstrate the effectiveness of the mask in reversing the signs of skin aging, a clinical study was conducted on 20 healthy Caucasian women: the antiwrinkle effect by measuring the depth of the crow's feet wrinkle, the relaxation of the oval of the face by clinical scoring, the firmness and elasticity of the skin by cutometric measurement, the density of the dermis by ultrasound analysis, the smoothness of the skin by measuring the roughness at the cheek, the homogeneity of the complexion by chromametric measurement, the diameter of the pores by macrophotographs and finally the sebo-regulating effect by measurement of the rate of sebum and quantification of the number of pores containing porphyrin in the subjects presenting a mixed to oily skin. The satisfaction of the volunteers was also evaluated at the end of the study via a self-questionnaire. RESULTS: The efficacy results measured after 1, 2, and 3 months of use are progressive and confirm the interest of LED photobiomodulation to reverse the visible signs of skin aging. All the volunteers observed an overall improvement in skin quality. CONCLUSION: All the results observed confirm the interest of using photobiomodulation to reverse the visible signs of aging. These results last for up to 1 month after stopping the use of the mask, which is a sign of lasting structural and functional rejuvenation of the skin.

Androgenetic alopecia in transgender and gender diverse populations: A review of therapeutics.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

Photobiomodulation for the treatment of neuroinflammation: A systematic review of controlled laboratory animal studies.

Background: Neuroinflammation is a response that involves different cell lineages of the central nervous system, such as neurons and glial cells. Among the non-pharmacological interventions for neuroinflammation, photobiomodulation (PBM) is gaining prominence because of its beneficial effects found in experimental brain research. We systematically reviewed the effects of PBM on laboratory animal models, specially to investigate potential benefits of PBM as an efficient anti-inflammatory therapy. Methods: We conducted a systematic search on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: photobiomodulation, low-level laser therapy, brain, neuroinflammation, inflammation, cytokine, and microglia. Data search was limited from 2009 to June 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The initial systematic search identified 140 articles. Among them, 54 articles were removed for duplication and 59 articles by screening. Therefore, 27 studies met the inclusion criteria. Results: The studies showed that PBM has anti-inflammatory properties in several conditions, such as traumatic brain injury, edema formation and hyperalgesia, ischemia, neurodegenerative conditions, aging, epilepsy, depression, and spinal cord injury. Conclusion: Taken together, these results indicate that transcranial PBM therapy is a promising strategy to treat brain pathological conditions induced by neuroinflammation.

Modulation of the autonomic nervous system by one session of spinal low-level laser therapy in patients with chronic colonic motility dysfunction.

Patients with a defecation disorder may not evoke a normal defecation reflex, or the reflex may be excessive, as a dysfunction of the spinal autonomic nervous system. Treatment with various forms of lumbar and sacral neuromodulation have shown symptom improvement, but potential changes in autonomic functioning are rarely studied. Here we evaluate the effects on autonomic function of a single session of low-level laser therapy (LLLT) on the lumbar and sacral spine in 41 patients with chronic gastrointestinal motor dysfunction. The LLLT protocol used red LED light at a wavelength of 660 nm for 10 min and infrared LED light at a wavelength of 840 nm for 10 min, followed by infrared laser light at a wavelength of 825 nm for 10 min. Effects on the autonomic nervous system were assessed by measuring heart rate variability (HRV) changes. Respiratory Sinus Arrhythmia (RSA) and Root Mean Square of Successive Differences (RMSSD) were used to quantify parasympathetic reactivity; the Baevsky's Stress Index (SI) reflected sympathetic activity while the ratios SI/RSA and SI/RMSSD were used to show shifts in autonomic dominance. The results indicate that lumbar and sacral neuromodulation using light arrays reduced, whereas stimulation by the laser probes significantly increased parasympathetic activity. The light arrays increased whereas the laser probes significantly decreased sympathetic activity (SI). The entire protocol shifted the autonomic balance toward parasympathetic activity. The comparison of actual vs. sham neuromodulation proved that the change in HRV parameters was due to actual light stimulation and not due to the arrays and probe touching the skin. In conclusion, a single session of LLLT markedly affects autonomic nervous system activity reflected in changes in HRV which is only possible by generating activity in the spinal autonomic nerves. These results warrant a study into the effects of LLLT on restoring autonomic dysfunction in chronic refractory colonic motility disorders.

Clinical Efficacy of Photobiomodulation on Dental Implant Osseointegration: A Systematic Review.

BACKGROUND: Photobiomodulation (PBM) has been shown to have a positive effect on dental implant osseointegration and stability in in vitro and animal studies; however, its usefulness in dental implant clinical practice is yet unclear. OBJECTIVE: The objective was to assess the clinical effectiveness of PBM on dental implants' osseointegration. METHODS: Two reviewers independently conducted a comprehensive electronic search of articles published from inception up to January 10, 2020, in PubMed, Cochrane Library and Embase databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized clinical trials (RCTs) and nonrandomized clinical studies that compared the effect of PBM on dental implant stability with control groups were included. Animals and in vitro studies studies as well as studies with confounders such as application of orthodontic were excluded. Risk of bias (using Cochrane Risk of Bias tool for RCTs and Risk of Bias in Non-Randomized Studies of Interventions tool for nonrandomized studies) was assessed by both authors. Owing to substantial heterogeneity, only a narrative synthesis of the included studies is presented. RESULTS: Seven relevant clinical studies were included, and they used a variety of PBM parameters and devices. The posterior region of the jaw was found to be more frequently evaluated. For assessing the effect of PBM on implant stability, five studies used resonance frequency analysis and two used periotest; three studies additionally used biomarkers for assessment. Four studies found that PBM has a potential positive effect on the outcome of dental implant stability, whereas three studies reported that PBM has no effect on implant stability. CONCLUSION: The findings of this systematic review suggest that postoperative application of PBM may potentially have some positive effect on dental implant's osseointegration and stability. However, additional studies are required with uniformity in methods to provide a more robust assessment of this effect.

Photobiomodulation does not influence maturation and mildly improves functional healing of mouse achilles tendons.

Tendon rupture can occur at any age and is commonly treated nonoperatively, yet can result in persisting symptoms. Thus, a need exists to improve nonoperative treatments of injured tendons. Photobiomodulation (PBM) therapy has shown promise in the clinic and is hypothesized to stimulate mitochondrial-related metabolism and improve healing. However, the effect of PBM therapy on mitochondrial function during tendon maturation and healing are unknown, and its effect on tendon structure and function remain unclear. In this study, near-infrared light (980:810 nm blend, 2.5 J/cm2 ) was applied at low (30 mW/cm2 ) or high (300 mW/cm2 ) irradiance to unilateral Achilles tendons of CD-1 mice during postnatal growth (maturation) as well as adult mice with bilateral Achilles tenotomy (healing). The chronic effect of PBM therapy on tendon structure and function was determined using histology and mechanics, and the acute effect of PBM therapy on mitochondrial-related gene expression was assessed. During maturation and healing, collagen alignment, cell number, and nuclear shape were unaffected by chronic PBM therapy. We found a sex-dependent effect of PBM therapy during healing on mechanical outcomes (eg, increased stiffness and Young's modulus for PBM-treated females, and increased strain at ultimate stress for PBM-treated males). Mitochondria-related gene expression was marginally influenced by PBM therapy for both maturation and healing studies. This study was the first to implement PBM therapy during both growth and healing of the murine tendon. PBM therapy resulted in marginal and sex-dependent effects on the murine tendon. Clinical significance: PBM may be beneficial for tendon healing because functional remodeling improves without adverse effects.

Transcranial Photobiomodulation to Improve Cognition in Gulf War Illness.

Introduction: Approximately 25-30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI. Materials and Methods: Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD. Results: Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (p < 0.01); and a trend for Trails 4, Number/Letter Sequencing (p < 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (p < 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed. Conclusion: This study was underpowered (n = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01782378.

Efficacy of low-level laser therapy associated with fluoride therapy for the desensitisation of molar-incisor hypomineralisation: Randomised clinical trial.

BACKGROUND: Molar-incisor hypomineralisation (MIH) is a qualitative enamel defect. AIM: To investigate the low-level laser therapy (LLLT) associated with fluoride varnish for the desensitisation of teeth with MIH. DESIGN: A randomised clinical trial was conducted with 66 children, randomly allocated to the treatments: laser (L); fluoride varnish (FV); and laser + fluoride varnish (L + FV). The participants in the L group underwent two sessions of LLLT (48-hour interval). The FV group received four applications of varnish at one-week intervals. The L + FV underwent two sessions of LLLT and four applications of varnish. Prior to each session and one month after the onset of treatment, tooth sensitivity and its magnitude were evaluated. Intra- and inter-group comparisons were performed (α = 5%). RESULTS: A significant reduction in the mean sensitivity score was found over time in all groups. After the final treatment, a significant difference was found between the L and L + FV groups (P = .011), with a lower score in the L + FV group (0.09), whereas no difference was found between the FV and L + FV groups (P = .095). CONCLUSIONS: Fluoride varnish and the combination of treatments (L + FV) had greater desensitising action on teeth with MIH. Laser therapy demonstrated an immediate desensitising effect, whereas fluoride varnish had a late-onset effect.

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.

Photobiomodulation improves the frontal cognitive function of older adults.

OBJECTIVES: The frontal lobe hypothesis of age-related cognitive decline suggests that the deterioration of the prefrontal cortical regions that occurs with aging leads to executive function deficits. Photobiomodulation (PBM) is a newly developed, noninvasive technique for enhancing brain function, which has shown promising effects on cognitive function in both animals and humans. This randomized, sham-controlled study sought to examine the effects of PBM on the frontal brain function of older adults. METHODS/DESIGNS: Thirty older adults without a neuropsychiatric history performed cognitive tests of frontal function (ie, the Eriksen flanker and category fluency tests) before and after a single 7.5-minute session of real or sham PBM. The PBM device consisted of three separate light-emitting diode cluster heads (633 and 870 nm), which were applied to both sides of the forehead and posterior midline, and delivered a total energy of 1349 J. RESULTS: Significant group (experimental, control) × time (pre-PBM, post-PBM) interactions were found for the flanker and category fluency test scores. Specifically, only the older adults who received real PBM exhibited significant improvements in their action selection, inhibition ability, and mental flexibility after vs before PBM. CONCLUSIONS: Our findings support that PBM may enhance the frontal brain functions of older adults in a safe and cost-effective manner.

Pain management using photobiomodulation: Mechanisms, location, and repeatability quantified by pain threshold and neural biomarkers in mice.

Photobiomodulation (PBM) is a simple, efficient and cost-effective treatment for both acute and chronic pain. We previously showed that PBM applied to the mouse head inhibited nociception in the foot. Nevertheless, the optimum parameters, location for irradiation, duration of the effect and the mechanisms of action remain unclear. In the present study, the pain threshold in the right hind paw of mice was studied, after PBM (810 nm CW laser, spot size 1 or 6 cm2 , 1.2-36 J/cm2 ) applied to various anatomical locations. The pain threshold, measured with von Frey filaments, was increased more than 3-fold by PBM to the lower back (dorsal root ganglion, DRG), as well as to other neural structures along the pathway such as the head, neck and ipsilateral (right) paw. On the other hand, application of PBM to the contralateral (left) paw, abdomen and tail had no effect. The optimal effect occurred 2 to 3 hours post-PBM and disappeared by 24 hours. Seven daily irradiations showed no development of tolerance. Type 1 metabotropic glutamate receptors decreased, and prostatic acid phosphatase and tubulin-positive varicosities were increased as shown by immunofluorescence of DRG samples. These findings elucidate the mechanisms of PBM for pain and provide insights for clinical practice.

Various Wavelengths of Light-Emitting Diode Light Regulate the Proliferation of Human Dermal Papilla Cells and Hair Follicles via Wnt/ß-Catenin and the Extracellular Signal-Regulated Kinase Pathways.

BACKGROUND: The human dermal papilla cells (hDPCs) play an important role in regulation of hair cycling and growth. OBJECTIVE: The aim of this study was to investigate the effect of different wavelengths of light-emitting diode (LED) irradiation on the proliferation of cultured hDPCs and on the growth of human hair follicles (HFs) in vitro. METHODS: We examined the effect of LED irradiation on Wnt/ß-catenin signaling and mitogen-activated protein kinase (MAPK) pathways in hDPCs. Anagen HFs were cultured with LED irradiation and elongation of each hair shaft was measured. RESULTS: The most potent wavelength in promoting the hDPC proliferation is 660 nm and 830 nm promoted hDPC proliferation to a lesser extent than 660 nm. Various wavelengths significantly increased ß-catenin, Axin2, Wnt3a, Wnt5a and Wnt10b mRNA expression. LED irradiation significantly increased ß-catenin and cyclin D expression, and the phosphorylation of MAPK and extracellular signal-regulated kinase (ERK). HFs irradiated with 415 nm and 660 nm grew longer than control. CONCLUSION: Our result suggests that LED has a potential to stimulate hDPC proliferation via the activation of Wnt/ß-catenin signaling and ERK pathway. To our best knowledge, this is the first report which investigated that the effect of various wavelengths of LED on hDPC proliferation and the underlying mechanisms.

Various Wavelengths of Light-Emitting Diode Light Regulate the Proliferation of Human Dermal Papilla Cells and Hair Follicles via Wnt/β-Catenin and the Extracellular Signal-Regulated Kinase Pathways

BACKGROUND: The human dermal papilla cells (hDPCs) play an important role in regulation of hair cycling and growth. OBJECTIVE: The aim of this study was to investigate the effect of different wavelengths of light-emitting diode (LED) irradiation on the proliferation of cultured hDPCs and on the growth of human hair follicles (HFs) in vitro. METHODS: We examined the effect of LED irradiation on Wnt/β-catenin signaling and mitogen-activated protein kinase (MAPK) pathways in hDPCs. Anagen HFs were cultured with LED irradiation and elongation of each hair shaft was measured. RESULTS: The most potent wavelength in promoting the hDPC proliferation is 660 nm and 830 nm promoted hDPC proliferation to a lesser extent than 660 nm. Various wavelengths significantly increased β-catenin, Axin2, Wnt3a, Wnt5a and Wnt10b mRNA expression. LED irradiation significantly increased β-catenin and cyclin D expression, and the phosphorylation of MAPK and extracellular signal-regulated kinase (ERK). HFs irradiated with 415 nm and 660 nm grew longer than control. CONCLUSION: Our result suggests that LED has a potential to stimulate hDPC proliferation via the activation of Wnt/β-catenin signaling and ERK pathway. To our best knowledge, this is the first report which investigated that the effect of various wavelengths of LED on hDPC proliferation and the underlying mechanisms.

Shining light on the head: Photobiomodulation for brain disorders.

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.

Low-level Light/Laser Therapy in Dermatology / 대한피부과학회지

Low-level laser or light therapy (LLLT) was used to accelerate wound healing without the use of thermal effects in the early days. Although the exact mechanism of LLLT is still unclear, it has been recognized as a photobiomodulation process. Today, LLLT is being credited as a non-invasive treatment modality, and in particular, being widely applied in the field of dermatology. In this review, we summarize the basic principles and clinical applications of LLLT to provide an up-to-date guidance on its practical and safe uses. Further studies are needed to elucidate the mechanism of action of LLLT in various indications, and to determine the wavelength and dose for optimal clinical use.

Drug discovery for alopecia: gone today, hair tomorrow.

INTRODUCTION: Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. AREAS COVERED: In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8(+)NK group 2D-positive (NKG2D(+)) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. EXPERT OPINION: The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.

Superpulsed (Ga-As, 904 nm) low-level laser therapy (LLLT) attenuates inflammatory response and enhances healing of burn wounds.

Low-level laser therapy (LLLT) using superpulsed near-infrared light can penetrate deeper in the injured tissue and could allow non-pharmacological treatment for chronic wound healing. This study investigated the effects of superpulsed laser (Ga-As 904 nm, 200 ns pulse width; 100 Hz; 0.7 mW mean output power; 0.4 mW/cm(2) average irradiance; 0.2 J/cm(2) total fluence) on the healing of burn wounds in rats, and further explored the probable associated mechanisms of action. Irradiated group exhibited enhanced DNA, total protein, hydroxyproline and hexosamine contents compared to the control and silver sulfadiazine (reference care) treated groups. LLLT exhibited decreased TNF-α level and NF-kB, and up-regulated protein levels of VEGF, FGFR-1, HSP-60, HSP-90, HIF-1α and matrix metalloproteinases-2 and 9 compared to the controls. In conclusion, LLLT using superpulsed 904 nm laser reduced the inflammatory response and was able to enhance cellular proliferation, collagen deposition and wound contraction in the repair process of burn wounds. Photomicrographs showing no, absence inflammation and faster wound contraction in LLLT superpulsed (904 nm) laser treated burn wounds as compared to the non-irradiated control and silver sulfadiazine (SSD) ointment (reference care) treated wounds.

Arrest of progression of pre-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice by low level laser phototherapy.

BACKGROUND AND OBJECTIVES: Using non-invasive, high-frequency ultrasonography (HF-u/s), we showed that low-level laser phototherapy (LLL) inhibits de-novo formation of abdominal aortic aneurysms (AAA) in apolipoprotein-E-deficient (Apo-E(-/-)) mice. The current study tests the effect of LLL on the progression of pre-induced AAA. STUDY DESIGN/MATERIAL AND METHODS: AAA was induced in Apo-E(-/-) mice (age 16-20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF-u/s (40 MHz, 0.01 mm resolution, Vevo-770, VisualSonics) was used to measure the maximum cross-sectional-diameter (MCD) of the suprarenal abdominal aorta, the anterior wall displacement (AWD), and radial wall velocity (RWV). The aortas of mice that developed >35% dilatation at 2 weeks over baseline were exposed retroperitoneally and treated with LLL (780 nm, 2.2 J/cm(2), 9 minutes) or sham-operated. HF-u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology. RESULTS: Of all mice with >35% MCD expansion of the suprarenal aorta at 2 weeks, 7(58%) of 12 non-treated, but only 1(7%) of 14 LLL, had increased MCD(> 1 SD) at 4 weeks (P < 0.009 by Fisher's Exact Test [FET]). The mean change in MCD from 2-4 weeks was also markedly reduced in the LLL-treated mice (control vs. LLL, 0.24 ± 0.25 vs. -0.06 ± 0.39 mm, P = 0.029 by unpaired t-test). Similar results were obtained when limiting the analysis to animals with ≥ 50% expansion at 2 weeks. The deterioration in AWD from 2-4 weeks in non-treated controls was not observed in LLL-treated animals (ΔAWD: control, 0.03 ± 0.05 mm, P < 0.036 vs. LLL, 0.00 ± 0.05, P = 0.91 by paired t-test). By the modified Daugherty classification, we found significantly fewer severe aneurysms at 4 weeks in the LLL-treated animals versus control (3 of 10 vs. 9 of 11, P = 0.03 by FET). CONCLUSIONS: LLL not only prevents de novo development of AAA, but, from this study, also arrests further progression of pre-induced AAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo-E(-/-) mice.