Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review.

Preclinical and clinical studies have indicated that combining photobiomodulation (PBM) therapy with other therapeutic approaches may influence the treatment process in a variety of disorders. The purpose of this systematic review was to determine whether PBM-combined therapy provides additional benefits over monotherapies in neurologic and neuropsychiatric disorders. In addition, the review describes the most commonly used methods and PBM parameters in these conjunctional approaches.To accomplish this, a systematic search was conducted in Google Scholar, PubMed, and Scopus databases through January 2024. 95 potentially eligible articles on PBM-combined treatment strategies for neurological and neuropsychological disorders were identified, including 29 preclinical studies and 66 clinical trials.According to the findings, seven major categories of studies were identified based on disease type: neuropsychiatric diseases, neurodegenerative diseases, ischemia, nerve injury, pain, paresis, and neuropathy. These studies looked at the effects of laser therapy in combination with other therapies like pharmacotherapies, physical therapies, exercises, stem cells, and experimental materials on neurological disorders in both animal models and humans. The findings suggested that most combination therapies could produce synergistic effects, leading to better outcomes for treating neurologic and psychiatric disorders and relieving symptoms.These findings indicate that the combination of PBM may be a useful adjunct to conventional and experimental treatments for a variety of neurological and psychological disorders.

Transcranial photobiomodulation mitigates learning and memory impairments induced by hindlimb unloading in a mouse model of microgravity exposure by suppression of oxidative stress and neuroinflammation signaling pathways.

Prolonged microgravity exposure causes cognitive impairment. Evidence shows that oxidative stress and neuroinflammation are involved in the causation. Here, we explore the effectiveness of transcranial near-infrared photobiomodulation (PBM) on cognitive deficits in a mouse model of simulated microgravity. 24 adult male C57BL/6 mice were assigned into three groups (8 in each); control, hindlimb unloading (HU), and HU + PBM groups. After surgery to fit the suspension fixing, the animals were housed either in HU cages or in their normal cage for 14 days. The mice in the HU + PBM group received PBM (810 nm laser, 10 Hz, 8 J/cm2) once per day for 14 days. Spatial learning and memory were assessed in the Lashley III maze and hippocampus tissue samples were collected to assess oxidative stress markers and protein expression of brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2), Sirtuin 1 (Sirt1), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Behavioral testing showed that the PBM-treated animals had a shorter latency time to find the target and fewer errors than the HU group. PBM decreased hippocampal lipid peroxidation while increasing antioxidant defense systems (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to HU mice. PBM increased protein expression of Sirt1, Nrf2, and BDNF while decreasing NF-κB compared to HU mice. Our findings suggested that the protective effect of PBM against HU-induced cognitive impairment involved the activation of the Sirt1/Nrf2 signaling pathway, up-regulation of BDNF, and reduction of neuroinflammation and oxidative stress in the hippocampus.

Synergistic effects of combined therapy with transcranial photobiomodulation and enriched environment on depressive- and anxiety-like behaviors in a mice model of noise stress.

The development of anxiety and depression due to chronic exposure to noise stress has remained as an unsolved health problem so far. Despite the studies suggesting the neuroenhancement effects of transcranial photobiomodulation (tPBM) and housing in an enriched environment (EE), the combined effects of these treatments have not been elucidated yet. Also, there is no available data on the relationship between the application of tPBM and hippocampal brain-derived neurotrophic factor (BDNF) expression in animal models of stress. The present study aims to investigate the application of the tPBM and EE (alone or in combination) on depressive- and anxiety-like behaviors in a mice model of noise stress. Mice were divided into five groups: control, noise, noise + EE, noise + tPBM, and noise + EE + tPBM. Except for the control group, other groups were subjected to 110 dB SPL white noise for 4 h/day for 14 consecutive days and received their respective treatments. Forced Swimming Test (FST) was used to evaluate depressive-like behaviors. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. BDNF, tyrosine receptor kinase B (TrkB), and cAMP response element-binding (CREB) protein levels in the hippocampus were determined by the Western blot method, and also serum corticosterone levels were assessed using an ELISA kit. Exposure to noise stress significantly elevated serum corticosterone level; downregulated hippocampal BDNF, TrkB, and CREB protein expressions; and resulted in depressive- and anxiety-like behaviors. While, the application of tPBM (810 nm wavelength, 8 J/cm2 fluence, 10 Hz pulsed wave mode), housing in EE, and their combination lowered corticosterone levels, upregulated the BDNF/TrkB/CREB signaling pathway in the hippocampus, and improved behavioral outcomes in noise stress subjected mice. Our finding revealed the improving effects of tPBM and EE on depressive and anxiety-like behaviors induced by noise stress, possibly by augmenting the BDNF/TrkB/CREB signaling pathway.

Effect of transcranial near-infrared photobiomodulation on cognitive outcomes in D-galactose/AlCl3 induced brain aging in BALB/c mice.

Brain photobiomodulation (PBM) therapy (PBMT) modulates various biological and cognitive processes in senescence rodent models. This study was designed to investigate the effects of transcranial near-infrared (NIR) laser treatment on D-galactose (D-gal)/aluminum chloride (AlCl3) induced inflammation, synaptic dysfunction, and cognitive impairment in mice. The aged mouse model was induced by subcutaneously injecting D-gal (60 mg/kg/day) followed by intragastrically administering AlCl3 (200 mg/kg/day) for 2 months. NIR PBM (810 nm laser, 32, 16, and 8 J/cm2) was administered transcranially every other day (3 days/week) for 2 months. Social, contextual, and spatial memories were assessed by social interaction test, passive avoidance test, and Lashley III maze, respectively. Then, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and synaptic markers including growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), and synaptophysin (SYN) levels were measured in the hippocampus using western blot method. Behavioral results revealed that NIR PBM at fluencies of 16 and 8 J/cm2 could reduce D-gal/AlCl3 impaired social and spatial memories. Treatment with NIR attenuated neuroinflammation through down-regulation of TNF-α and IL-6. Additionally, NIR significantly inhibited the down-regulation of GAP-43 and SYN. The results indicate that transcranial PBM at the fluencies 16 and 8 J/cm2 effectively prevents cognitive impairment in mice model of aging by inhibiting the production of the inflammatory cytokines and enhancing synaptic markers.