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A Protocol for Transcranial Photobiomodulation Therapy in Mice

Transcranial photobiomodulation is a potential innovative noninvasive therapeutic approach for improving brain bioenergetics, brain function in a wide ...

Tabriz University of Medical Sciences

ProNeuroLIGHT LLC

The application of transcranial low-level light/laser therapy (tLLLT) in the range of red to near-infrared (NIR) spectrum for psychological disorders is a new area that is attracting growing interest in recent years. The photomodulation effects of NIR and red coherent lights on the activity of cytochrome c oxidase in neuronal cells of brain have been recently introduced. This study, therefore, sought to compare the therapeutic effects of 10-Hz pulsed wave NIR (810 nm) laser with red (630 nm) laser using the same delivered energy density and Citalopram in rat chronic mild stress (CMS) model of depression and anxiety.

Therapeutic effects of 10-HzPulsed wave lasers in rat depression model: A comparison between near-infrared and red wavelengths.

Mitochondrial function plays a key role in the aging-related cognitive impairment, and photoneuromodulation of mitochondria by transcranial low-level laser therapy (LLLT) may contribute to its improvement. This study focused on the transcranial LLLT effects on the D-galactose (DG)-induced mitochondrial dysfunction, apoptosis, and cognitive impairment in mice. For this purpose, red and near-infrared (NIR) laser wavelengths (660 and 810 nm) at 2 different fluencies (4 and 8 J/cm) at 10-Hz pulsed wave mode were administrated transcranially 3 d/wk in DG-received (500 mg/kg/subcutaneous) mice model of aging for 6 weeks. Spatial and episodic-like memories were assessed by the Barnes maze and What-Where-Which (WWWhich) tasks. Brain tissues were analyzed for mitochondrial function including active mitochondria, adenosine triphosphate, and reactive oxygen species levels, as well as membrane potential and cytochrome c oxidase activity. Apoptosis-related biomarkers, namely, Bax, Bcl-2, and caspase-3 were evaluated by Western blotting method. Laser treatments at wavelengths of 660 and 810 nm at 8 J/cmattenuated DG-impaired spatial and episodic-like memories. Also, results showed an obvious improvement in the mitochondrial function aspects and modulatory effects on apoptotic markers in aged mice. However, same wavelengths at the fluency of 4 J/cmhad poor effect on the behavioral and molecular indexes in aging model. This data indicates that transcranial LLLT at both of red and NIR wavelengths at the fluency of 8 J/cmhas a potential to ameliorate aging-induced mitochondrial dysfunction, apoptosis, and cognitive impairment.

Transcranial low-level laser therapy improves brain mitochondrial function and cognitive impairment in D-galactose-induced aging mice.

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.

Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice.

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 Caand 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.

Brain Photobiomodulation Therapy: a Narrative Review.

Medial prefrontal cortex (mPFC) ischemia affects post-stroke cognitive outcomes. We aimed to investigate the effects of different doses and routes of cerebrolysin (CBL) on the structural synaptic plasticity and cognitive function after mPFC ischemia in mice. Thence, CBL (1, 2.5 ml/kg/i.p./daily) or (1 ml/kg/i.n./daily), were administrated in photothrombotic mouse model of mPFC ischemia for two weeks. Episodic and spatial memories were assessed by the What-Where-Which (WWWhich) and Barnes tasks. Growth-associated protein 43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptophysin (SYN) levels were measured in the lesioned area using western blot analysis. Dendritic arbors, spine densities, and morphology were assessed via Golgi-Cox staining. Treatment with 2.5 ml/kg/i.p. and 1 ml/kg/i.n. doses attenuated mPFC ischemia-induced episodic and spatial memories impairment. Results showed an obvious increase in the GAP-43, PSD-95 and SYN levels and improvement in the structural synaptic indexes in lesioned area induced by the same doses and routes of CBL. In conclusion, we found that specific doses/routes of CBL have positive effects on the structural synaptic plasticity and cognitive outcomes after mPFC ischemia.

Intranasal cerebrolysin improves cognitive function and structural synaptic plasticity in photothrombotic mouse model of medial prefrontal cortex ischemia.

Chronic stress has been linked to the pathophysiology of mood disorders including anxiety and depression. In this study, we aimed to investigate the effect of troxerutin (TRX), as a flavonol, on stress-induced anxiety and depression.

Effects of troxerutin on anxiety- and depressive-like behaviors induced by chronic mild stress in adult male rats.

This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q (CoQ) 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/cm) and/or CoQ (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 CoQ, 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 CoQ 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 CoQ 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 CoQ therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.

Near-Infrared Photobiomodulation Combined with Coenzyme Q for Depression in a Mouse Model of Restraint Stress: Reduction in Oxidative Stress, Neuroinflammation, and Apoptosis.

Farzad Salehpour

Neurosciences Research Center

Tabriz University of Medical Sciences

A Protocol for Transcranial Photobiomodulation Therapy in Mice