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 of most concern to humans in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: sudden 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, autism). 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”. Transcranial LED light sources are ideally suited to be home use devices. 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.

Spinal cord injury (SCI) can result in shortened life expectancy and prohibiting lifelong medical costs. Low-level light therapy (LLLT) is currently showing promise for SCI treatment in animal models. Despite the promising attributes of LLLT for SCI treatment, there is still a lack of standardized experimental protocol(s), which makes it difficult to compare results. In this paper we describe our Monte-Carlo simulation results of light propagation in a spinal cord injured rat model with different illumination parameters. This study provides an efficient approach to guide researchers in optimizing illumination parameters and aid towards quantitative and qualitative standardization of LLLT-SCI treatment.

Photobiomodulation has been reported to be beneficial for the treatment of neuropathic pain. However, laser penetration characteristics from skin to nerve have yet to be fully elucidated. In this study, we implanted photo-sensors near lumbosacral nerves of rats, irradiated laser (wavelength: 808 and 830 nm; output: 2, 5 and 10 W pulse) transcutateously, and took micro-CT images of rats to determine the fluence rate at the lumbosacral nerves. The results showed that the fluence rate at the lumbosacral nerves was 179±19.2 mW/cm2 and 232±20.7 mW/cm2 when the 808 nm and 830 nm laser was irradiated at 10 W respectively.

Low-level lighy therapy (LLLT) using LED on the status epilepticus has been unknown. Status epilepticus is the serious neurological diseases, leading to severe and widespread cell damage in the brain. This study suggests that photomodulation using LLLT at 660 nm can be useful for preventing neurodegenerative diseases, especially status epilepticus.

Photobiomodulation therapy of spinal cord injury has significant potential; however, it is unknown whether it is possible to safely deliver a clinically effective photobiomodulatory dose to the spinal cord with clinically acceptable, non-invasive, treatment protocols. We developed a flexible, multi-channel photo-detector applicator-probe for multi-site dosimetry in the spinal canal of a dog model. The probe, with a 1/4" stem, contains 9 photo-diodes spaced 1cm apart allowing measurement of irradiance over an 8cm length. Multi-site dosimetry at 980nm was tested by deploying the applicator-probe in the spinal canal of a cadaver dog at a surface (shaved skin) irradiance of 3.18 W/cm2.

In our study, we used functional near-infrared spectroscopy (fNIRS) and venous-occlusion plethysmography to measure the LLLT-induced changes in blood flow, oxygenation, and oxygen consumption in human forearms in vivo. Eight participants were administered with 810-nm light. We found that LLLT induced a significant increase of blood flow and oxygen consumption on the treated site. Meanwhile, LLLT took a good role in promoting oxygenation of regional tissue, which was indicated by an increase of oxygenated hemoglobin concentration, a decrease of deoxygenated hemoglobin concentration. These results not only demonstrate enormous potential of LLLT, but help to figure out mechanisms of photobiomodulation.

Traumatic brain injury (TBI) is a major cause of death and disability in the US. Recently we proposed Nano Pulse Laser Therapy (NPLT) for therapy of TBI and other disorders and developed and built a novel, medical grade NPLT system generating high-energy nanosecond NIR pulses. In this study we tested the ability of NPLT to reduce the activation of microglia (which plays a crucial role in systemic long term inflammation) in a rat model of TBI. Our results show that a 5-minute transcranial application of NPLT significantly reduces the activation of microglia and prevents brain volume loss after TBI.

The mechanisms of Photobiomodulation start with absorption of a photon by a molecule, that triggers an intracellular cascade followed by some extracellular signalling. Extracellular messengers get into interstitial fluids, blood or lymph and can travel some distance to initiate some remote effects. Photobiomodulation treatment of nerve roots have an effect on peripheral pain, transcutaneous treatment of bone marrow releases mesenchymal stem cells, treatment of lymph nodes reduce edema, treatment of one limb improves blood flow in the contralateral limb. This review summaries the evidence for indirect and distant effects of Photobiomodulation and discusses how clinically meaningful they may be.

In our previous in vivo studies we pointed out that the blue light accelerates the differentiation of fibroblasts into myofibroblasts, improving collagen morphology and leading to a faster healing of the treated tissues. The purpose of the present work is to investigate the effects of blue light on fibroblasts and in the remodeling phase. We studied primary human cell cultures of both healthy and keloid fibroblasts, since keloid are one of the possible therapeutic targets and represent a model of hyperproliferation. Our results show that the blue light has a direct effect on fibroblasts. Future work will consist in testing the blue light in keloids in vivo, to demonstrate its efficacy and to define a possible range of applications.

Low level light therapy (LLLT) using light from red and near infrared LEDs or Lasers have been reported effective as noninvasive methods for reducing spot fat. A total of 56 subjects were randomly divided into 26 test groups and 26 control groups for abdominal fat reduction clinical trial using red and near infrared LED phototherapy devices. Red and near infrared light with irradiance of 10 mW/cm2 were irradiated over the abdominal area to the test group for 30 minutes followed by 30 minutes of aerobic exercise, 3 times a week for 4 weeks. Control group used sham devices for 30 minutes and followed by 30 minutes of aerobic exercise. It was found that red and near infrared LED phototherapy combined with aerobic exercise would be effective and safe for abdominal fat reduction without any side effects.

The Photobiomodulation (PBM) using different wavelengths can be useful on Skin ageing and its treatment. Clinical study was performed in 5 groups: G1 - Control group (cosmetics); G2 - Light group (PBM with ambar light); G3 - Light group (PBM with ambar light +infrared light), G4 - Light group (cosmetics + PBM with ambar light), G5 - Light group (cosmetics + PBM with ambar light +infrared light). The results suggest that ambar light associated to infrared light improves the age spots and Tissue and Muscle Flaccidity reduction.

Myocardial ischemic reperfusion injury can result from the influx of oxygenated blood after heart attack or cardiac surgery and causes increased heart muscle damage. Photobiomodulation (PBM) has been shown to be effective in treatment of wounds and muscle damage, so it has potential as an intervention to prevent or limit cardiac damage. There is increasing evidence from animal and tissue models that PBM delivered either directly through the chest wall or to other distant body locations, can reduce cardiac damage and other complications of cardiac surgery, including delayed wound healing. Preliminary results of clinical trials will also be discussed.

We investigated the effect of photobiomodulation on lower urinary tract function in 3 groups including Sham-Group, Control-Group (acetic acid induced rat cystitis model) and Laser-Group (acetic acid induced rat cystitis model with 830nm laser irradiation). Voiding interval after laser irradiation in Laser-group tended to be longer than that in Control-Group. Bladder pressure parameters were not significant different among 3 groups. In sub-group analysis on voiding intervals, laser irradiation improved voiding interval and voiding volume more efficiently in shorter voiding interval group than longer voiding interval group. These data indicate that laser irradiation may improve urine storage function without loss of voiding function.

The aim of the present study was to assess, by Raman spectroscopy, the repair of complete surgical tibial fractures fixed with osteosynthesis or miniplates treated or not with infrared phototherapy associated or not to the use of MTA cement. Surgical fractures were created and fixed with WO or miniplates and some groups were grafted with MTA. The results showed that irradiation influenced the peaks of phosphate and carbonated hydroxyapatites. Collagen peak was influenced by both the use of MTA and irradiation. It is concluded that the use of phototherapy associated to MTA improved the repair of complete tibial fractures.

Can we treat ‘light as a drug’ for Photobiomodulation therapy? To satisfy the definition of an active pharmaceutical agent, the substance should be absorbed and capable of changing bodily function that light satisfies. Our understanding of our visual cycle and Vitamin D metabolism are clear evidences for this phenomenon. Advances in optophotonic technologies along with a better understanding of light-tissue interactions, especially in in vivo optical imaging and optogenetics, are spearheading the popularity of biophotonics in biology and medicine. This therapy is defined as the non-thermal use of non-ionizing forms of photonic devices including lasers, LEDs and broad-band light to alleviate pain, inflammation, modulate immune responses and promote wound healing and tissue regeneration. This presentation will provide a brief overview of the two most well understood phenomenon namely, an intracellular mechanism involving cytochrome c oxidase in the mitochondria and an extracellular mechanism involving activation of a latent growth factor, TGF-β1. Surprisingly, despite vast volumes of scientific literature from both clinical and laboratory studies noting the phenomenological evidences for this innovative therapy, there has been inconsistent, non-reproducible clinical outcomes. It is hoped that outlining the molecular mechanism will enable development of more robust, safe and efficacious PBM clinical regimens.

Photobiomodulation (PBM) refers to the effects of low doses of light, and while much is known about these beneficial outcomes, understanding of the underlying molecular mechanisms is still limited. Nitric oxide (NO) is a powerful signaling molecule and it is known that PBM can induce elevated levels of NO. Utilizing an in vitro model we have begun to systematically investigate the mechanism of NO production and function in the PBM response, focusing on wavelength-dependency, the role of nitric oxide synthases, and the electron transport chain. These results provide a roadmap for interrogating the molecular mechanisms of PBM and NO signaling.

The effect of near infrared light (940 nm) on the conversion of 5-aminolevulinic acid (5-ALA) to PpIX, a compound involved in photodynamic therapy (PDT), was examined. The back skin of two test subjects was irradiated with continuous wavelength and pulsed infrared light at 940 nm. These irradiations took place 50-53, 24-29, and 8-14 hours prior to the application of the 5-ALA. After a three hour incubation period with 5-ALA, a FluoDerm™device was used to measure the fluorescence of the skin (emitting wavelength: 400-420 nm; measuring excitation wavelength: 610-720 nm), a direct indication of the activity of 5-ALA. 5-ALA must penetrate the skin and then be converted to PpIX before any fluorescence increase can be observed. Results: Several pulsed and some CW conditions at 940 nm, up to 53 hours pre-irradiation, showed a statistically significant increase in fluorescence (p = 0.05) (Fluoderm™ readings), compared to the no-irradiation 5-ALA only control. Conclusion: This preconditioning method uses a temperature-independent mechanism of action via cell signaling pathways as in photobiomodulation. In this study, pulsing was superior to CW mode.

Photobiomodulation therapy has been around for several decades with a number of applications increasing every year. However, the exact mechanisms of energy/signal transduction, which lead to the observed changes and the lack of those in living cells, is still poorly understood. We proposed and experimentally implement a novel research platform, which uses microfluidic chip and controllable excitation condition to precisely initiate the process of photobiomodulation. Resonance Raman spectroscopy is employed to assess the structural transformational stages on different time-scales. We will present our first experimental results and will discuss those with respect to potential therapeutic applications.

Summary: Platelet Rich Plasma (PRP) injections are an effective treatment to reduce pain in most patients with arthritis in our experience, but some do not respond. These non-responding patients must often be treated with joint replacement surgery. We treated 29 patients who had had no response to initial PRP injection in the knee and other joints by the senior author (CP), with repeat PRP injection but this time augmented with simultaneous intra-articular laser treatment. Over 40% of these previously non-responding patients, who served as their own historical controls, had a good response to PRP-laser treatment. All have avoided surgery.

Laser acupuncture (LA) is a non-invasive and painless way to achieve some therapeutic effects. And compared to traditional acupuncture, LA is free from infection.We innovatively developed a portable laser acupuncture device with therapy part and detection part together. Therapy part sends out laser at the wavelength of 650 nm onto special acupoints of patients. And detection part includes integrated light-emitting diode (LED, 735/805/850 nm) and photodiode (OPT101). The detection part is used for the data collection for calculation of hemodynamic parameters based on near-infrared spectroscopy (NIRS).

Extraorally applied photons pass through the skin and muscle of the cheek to reach buccal mucosa. Reflection, scattering and absorption make tissue thickness and melanin concentration factors in the resulting power density. Subjects between 8 and 40 years were assigned a Fitzpatrick skin type score and tissue thickness was recorded. An LED array was applied to the external cheek. The power density at the intraoral mucosa was recorded. Power density reaching the intraoral mucosa was only five to ten percent of that applied to the external cheek. Tissue thickness and surface pressure were found to have an significant effect on transmission while skin tone did not. The possible cause of this unexpected result will be proposed and efforts to improve transmission of photonic energy will be discussed.

To study early metabolic responses to VIS/NIR laser light we performed kinetic analyses for Raman spectra in mitochondria isolated from mammalian cells. Raman excitation was at 532 nm and was expected to produce resonance spectra for cytochrome c. Raman spectra of mitochondria using pyruvate substrate were distinct from those using succinate, indicating our analysis distinguishes between electron transport originating at Complex I and Complex II. Reduction and oxidation (RedOx) levels of cytochrome c was a useful measure of effect upon VIS/NIR laser exposures. We present changes in Raman peak intensity and spectral shifts specific to electron transport chain substrate and laser wavelength (blue, red, NIR) of interrogation.

Recently, transcranial photobiomodulation (PBM) is proposed as an innovative modality for neuroenhancement. Present work focused on the mitochondrial protection of red and near-infrared (NIR) PBM against d-galactose induced brain aging in mice. Red (660 nm) and NIR (810 nm) lasers (at 4 and 8 J/cm2 and 10-Hz pulsed wave) were applied transcranially there day/week in d-galactose-received (500 mg/kg/subcutaneous) mice for six weeks. Transcranial PBM with red and NIR at 8 J/cm2 results in improvement of vital mitochondria, and increase in the mitochondrial membrane potential, cytochrome c oxidase activity and ATP production in the brain.

Physiological aging leads to dysfunction of the stomatognathic system. Photokinesiotherapy (PKT) is a program using photobiomodulation (PBM) in combination with different kinesiotherapies. PBM can slow down and manage aging process resulting in orofacial dermal-neuro-muscle rehabilitating. We are searching for a new more efficient therapy to decrease and manage velocity of senescence and disfuntion of stomatognathic system. Under Ethical Comittee approval (CAAE no. 45390715.2.0000.5419), fifteen female patients were selected and divided into 5 groups: Control, PBM, PBM+Exercises, PBM+Electrotherapy, PBM+kinesiotherapy. All treatments affected muscle tone, rebalancing the force vectors between the facial muscles, cutaneous elasticity and ecogenicity behaviour, resulting in interesting individual clinical observations. We suggest that PKT could be an efficient choice to orofacial rehabilitation.

Bacterial resistance to antibiotics is reality. We evaluated, in vitro, the effect of LED photochemotherapy on S. aureus using 25 μg / mL of phenothiazine combined with LED light using 12 J/cm². The experiments were carried out in triplicate and the samples were divided into groups: Control, Irradiated, Photosensitizer, LED-Photochemotherapy. Counts of the colony forming units and the data obtained were statistically analyzed. The present study demonstrated that the efficacy of LED-Photochemotherapy caused 91.57% of inhibition. It is concluded that using energy density of 12 J/cm² associated to 25 µg/mL caused high in vitro inhibition of S. aureus.

The use of nanoparticle on dental light cure resin is used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major targets for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at ~620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

Photobiomodulation therapy uses light from a laser and is, therefore, a non-invasive, non-thermal treatment that is effective in reducing chronic pain and inflammation, stimulating wound healing and tissue regeneration. Due to its accessibility and ease of use, it is also presently explored as an alternative to lipoplasty for fat removal. This review covers literature focusing on the applications of photo modulation therapy, with particular emphasis on the safety and efficacy of this therapy on fat loss. Moreover, additional studies demonstrating the efficacy of photo modulation therapy in larger groups would be helpful in establishing this technique for regular clinical use.