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

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This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q10 (CoQ10) on depressive-like behavior, cerebral oxidative stress, inflammation, and apoptosis markers in mice. To induce a depressive-like model, mice were subjected to sub-chronic restraint stress for 5 consecutive days. NIR PBM (810 nm laser, 33.3 J/cm2) and/or CoQ10 (500 mg/kg/day, gavage) were administered for five days concomitantly with immobilization. Behavior was evaluated by the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Mitochondrial membrane potential as well as oxidative stress, neuroinflammatory, and markers of apoptosis were evaluated in the prefrontal cortex (PFC) and hippocampus (HIP). The serum levels of pro-inflammatory cytokines, cortisol, and corticosterone were also measured. PBM or CoQ10, or the combination, ameliorated depressive-like behaviors induced by restraint stress as indicated by decreased immobility time in both the FST and TST. PBM and/or CoQ10 treatments decreased lipid peroxidation and enhanced total antioxidant capacity (TAC), GSH levels, GPx and SOD activities in both brain areas. The neuroinflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels in PBM and/or CoQ10 groups. Intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and −9, were also significantly down-regulated by both treatments. Furthermore, both treatments decreased the elevated serum levels of cortisol, corticosterone, TNF-, and IL-6 induced by restraint stress. Transcranial NIR PBM and CoQ10 therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.

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

This study showed that non-invasive tLLLT using 10-Hz pulsed NIR laser light was as effective as Citalopram and more effective than red laser in the treatment of depressive-like behaviors and may help improve tLLLT as an alternative non-pharmacological treatments of psychological disorders such as depression. Lasers Surg. Med. 48:695-705, 2016. © 2016 Wiley Periodicals, Inc.

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