Photobiomodulation as a regulator of neuroinflammation: mechanistic insights and therapeutic potential in brain disorders

Abstract

Brain disorders, including neurodegenerative, neuropsychiatric, and cerebrovascular diseases, represent a growing global health challenge contributing to disability and mortality worldwide. Although these conditions differ in etiology and clinical presentation, accumulating evidence identifies neuroinflammation as a shared pathological mechanism. Involving microglial activation, astrocytic reactivity, cytokine dysregulation, oxidative stress, mitochondrial dysfunction, and blood–brain barrier disruption, it contributes to synaptic dysfunction, neuronal loss, and disease progression, yet therapeutic strategies targeting these processes remain limited. Photobiomodulation (PBM), the therapeutic application of low-intensity red to near-infrared light, has emerged as a neurotechnology capable of modulating biological pathways relevant to neuroinflammation. Preclinical studies suggest that PBM may influence mitochondrial activity through cytochrome c oxidase-mediated mechanisms, enhancing cellular metabolism while regulating reactive oxygen species, inflammatory signaling pathways, and tissue homeostasis. Through these effects, PBM may attenuate neuroinflammatory responses, regulate glial activation, and support neuroprotective processes across multiple neurological models. This narrative review examines evidence supporting neuroinflammation as a common denominator across major brain disorders and explores the biological rationale for PBM as a therapeutic strategy. It summarizes the cellular and molecular basis of PBM, its effects on neuroinflammatory pathways, and preclinical and clinical findings across brain disease models. Preclinical findings consistently support a multi-target anti-inflammatory effect, whereas clinical investigation remains at an early stage, with encouraging results in Alzheimer’s disease and multiple sclerosis but mainly negative data on primary outcomes in Parkinson’s disease and major depressive disorder. Further research is needed to optimize treatment parameters, clarify mechanisms of action, and determine clinical efficacy across disease contexts.