Photobiomodulation in Stroke: Delivery, Dosimetry, and Clinical Validation

Stroke remains a leading cause of long-term disability, and neurorecovery options remain sparse. Photobiomodulation therapy (PBMT), the application of red and near-infrared light (600–1100 nm) to biological tissue, has emerged as a non-invasive, adjunctive, and promising modality. In PBMT, photons are absorbed by cellular chromophores, including ion channels and mitochondrial complexes, which are then activated to produce ATP, signaling molecules, and transcription factors instrumental in cellular cascades that promote healing. PBMT reduces inflammation, pain, and edema, and enhances cellular and tissue regeneration and blood flow. Preclinical work in stroke has shown that PBMT contributes to increased cerebral blood flow, modulation of inflammatory cytokines, release of neurotrophic factors (BDNF, NGF, GDNF), vascular growth and endothelial repair factors, and synaptic plasticity. In animal models of stroke, PBMT treatment led to neuroprotection, neuroplasticity, angiogenesis, and significant improvements in muscle resistance, physical function, and spatial and episodic memory.Translation to humans is challenging due to skull thickness, light scattering, brain volume, patient heterogeneity, and the inability to sample brain tissue directly. Clinical trials have produced mixed results, and the field lacks consensus on which delivery route, dose, and timing produce the desired PBMT effect and which biological targets are reached.This Research Topic aims to consolidate evidence across the three principal PBMT delivery routes in stroke (transcranial, glymphatic, and systemic/peripheral) and to advance validated, reproducible protocols for clinical use. A central obstacle is our inability to directly confirm cellular or tissue-level effects of PBMT in living patients. Plasma and exosomal proteomics combined with bioinformatics offer powerful, blood-based approaches that biopsy the brain environment to identify and quantify the signaling molecules, transcription factors, pathways, and cell types engaged by treatment.Recent studies using blood samples from stroke patients, comparing ischemic versus hemorrhagic stroke, RIC-treated versus untreated, and diabetic versus non-diabetic groups, have identified numerous differentially expressed serum biomarkers. Bioinformatic analysis has yielded data on biological processes, cellular components, and anatomical tissues, providing insight into neurogenesis, neuronal differentiation, synaptic function, and specific brain regions.We encourage groups conducting human PBMT studies to collect blood samples before, during, and after treatment, and to include sham and healthy controls. Established proteomics centers can perform the analyses without added labor for clinical teams, accelerating the molecular validation the field currently lacks.We welcome original research, systematic reviews, clinical trial reports, study protocols, and perspective articles addressing:• Transcranial PBMT: light penetration, fluence optimization, target tissue delivery• Glymphatic PBMT: mechanisms, feasibility, and translational potential in ischemic and hemorrhagic stroke• Systemic/peripheral PBMT: clinical and molecular effects following application to skin or limbs• Comparative analysis of delivery modalities for efficacy, safety, and clinical practicality• Dosimetric parameters: wavelength, power density, pulse frequency, irradiation duration, and timing relative to stroke onset• Plasma and exosomal proteomics, biomarkers, and outcome measures for PBMT trials• Clinical trial design, including sham controls, patient selection, and immune-neurological pathway analysisBy integrating delivery science with molecular validation, this collection aims to move PBMT in stroke from fragmented promise toward a coherent, clinically actionable framework. Topic editors: Mariana Vetrici, Praveen Arany Source: https://www.frontiersin.org/research-topics/81223/photobiomodulation-in-stroke-delivery-dosimetry-and-clinical-validation