Photobiomodulation (PBM) is a safe and effective neurotherapy that modulates cellular pathways by altering cell membrane potentials, leading to beneficial biological effects such as anti-inflammatory and neuroregenerative responses. This review compiles studies from PubMed up to March 2024, investigating the impact of light at wavelengths ranging from 620 to 1270 nm on ion channels. Out of 330 articles screened, 19 met the inclusion criteria. Research indicates that PBM can directly affect various ion channels by influencing neurotransmitter synthesis in neighboring cells, impacting receptors like glutamate and acetylcholine, as well as potassium, sodium channels, and transient receptor potential channels. The diversity of studies hampers a comprehensive meta-analysis for evaluating treatment strategies effectively. This systematic review aims to explore the potential role of optoelectronic signal transduction in PBM, studying the neurobiological mechanisms and therapeutic significance of PBM on ion channels. However, the lack of uniformity in current treatment methods underscores the necessity of establishing standardized and reliable therapeutic approaches. Graphical Abstract PBM is a promising neurotherapeutic approach with anti-inflammatory and neuroregenerative potential through its effects on cell membrane potential and ion channels. This systematic review analyzes 19 studies, revealing its influence on channel activity and emphasizing the need for standardized treatment protocols.

This systematic bibliometric analysis evaluates the scientific evidence, impact, and trends of photobiomodulation (PBM) for central nervous system (CNS) disorders. Analyzing 150 relevant PubMed-indexed studies (including 46 clinical trials) up to September 2024, we demonstrate PBM's positive effects on the CNS. Key mechanisms include enhanced ATP synthesis, modulated nitric oxide signaling, improved neuronal excitability, suppressed oxidative stress, anti-inflammatory effects, and ion channel modulation. PBM offers therapeutic flexibility: shorter-wavelength, high-irradiance power lasers effectively target deep brain structures, while both modalities suit superficial cortical applications where fine spatial control is nonessential.Crucially, PBM induces long-lasting biological effects, highlighting significant potential for chronic CNS conditions like Alzheimer's disease, Parkinson's disease, and stroke. However, critical challenges hinder translation: optimizing disease-specific wavelengths and light sources (laser vs. LED, continuous vs. pulsed), and establishing standardized, long-term treatment protocols based on robust dose-response relationships. Resolving heterogeneity in parameters (energy density, power, potential thermal effects) is paramount for PBM to become a reliable neuromodulation tool. This analysis provides critical insights for advancing targeted PBM therapies in CNS.

Glutamate receptors regulate neuronal excitability and drive synaptic plasticity in the auditory cortex (AC), with aberrant activation or dysfunction contributing to tinnitus pathogenesis. Photobiomodulation (PBM) exerts sustained modulatory effects on neural activity and behavioral responses across species, including humans. However, its therapeutic potential and mechanisms in noise-induced tinnitus remain unexplored. Here, we developed a noninvasive low-irradiance PBM device to target the AC of animal models, investigating near-infrared light mechanisms for reversing cortical hyperexcitability and restoring synaptic plasticity. In noise-exposed tinnitus models without significant neuronal loss, we observed abnormally elevated GluN1 activation and increased synaptic structural complexity compared to non-tinnitus or sham-exposed controls. Tinnitus models were subjected to PBM interventions with varying parameters (irradiance power: 20/40/80mW/cm²; exposure duration: 300/600s). Therapeutic efficacy was validated through auditory brainstem response (ABR), gap-prepulse inhibition of acoustic startle (GPIAS), and prepulse inhibition (PPI) behavioral assays. Fluorescence microscopy of brain sections quantified c-Fos/GluN1 co-localization to image activated NMDARs, while Nissl staining assessed PBM safety across parameters. Phosphoproteomic profiling explored mechanistic pathways, with neuronal morphological changes visualized via Golgi staining and transmission electron microscopy. To confirm GluN1's pivotal role in auditory cognition, we engineered transgenic mice with GluN1 overexpression or knockdown. GluN1-overexpressing mice exhibited tinnitus-like behaviors at specific frequencies, whereas GluN1-deficient tinnitus models showed aberrant behaviors due to impaired auditory cognition. Our findings delineate noise-induced tinnitus mechanisms and PBM-mediated regulation of neuronal excitability and structural plasticity, establishing an irradiance-duration optimization framework for clinical translation.

Tinnitus, a prevalent auditory symptom, can significantly impair quality of life, yet no definitive pharmacological interventions exist despite extensive o