Transcranial Photobiomodulation Ameliorates Cerebrovascular and Meningeal Lymphatic Dysfunction after Repetitive Concussion: A Multimodal Optical Study in Mice.

Abstract

RATIONALE AND OBJECTIVES: Repeated mild traumatic brain injury (mTBI), particularly from concussions, impairs cerebral perfusion and brain waste-clearance pathways, leading to lasting neurological deficits and elevated risk of neurodegeneration. Conventional pharmacological treatments targeting single pathways have shown limited efficacy in clinical trials. Photobiomodulation (PBM) has emerged as a promising noninvasive approach with the potential to improve both vascular function and clearance. AIM: To determine whether transcranial PBM at 1267&#xa0;nm, administered during the acute phase after repetitive concussion, improves cortical perfusion, oxygenation, intracranial compliance, meningeal lymphatic drainage, and neurological function in mice. MATERIALS AND METHODS: Male C57BL/6 mice (n=20) were randomized to PBM and sham groups and subjected to three repeated consecutive closed-head concussive impacts at 1.5-hour intervals to model repetitive mTBI. Transcranial PBM (1267&#xa0;nm, 10 mW/cm&#xb2;, 5&#xa0;mm diameter spot) was applied 4&#xa0;h after the last impact for 45&#xa0;min (three 10-minute sessions separated by 5-minute intervals). The 1267&#xa0;nm wavelength lies within a biological transparency window that supports deeper transcranial penetration than shorter near-infrared wavelengths. Outcomes included cortical microcirculation, tissue oxygenation, intracranial compliance, meningeal lymphatic drainage, and neurological severity score. Statistical analyses were performed using two-way analysis of variance for multiple comparisons, with p < 0.05 considered significant. RESULTS: Repetitive concussion produced stepwise declines in cortical perfusion and oxygenation, reduced cerebral compliance, impaired lymphatic clearance, and worse neurological scores. PBM partially reversed these deficits compared with sham, improving microcirculation and oxygenation toward baseline levels, increasing cerebral compliance, restoring meningeal lymphatic drainage, and lowering neurological severity scores. CONCLUSION: Acute transcranial PBM at 1267&#xa0;nm mitigates cerebrovascular, biomechanical, and meningeal lymphatic dysfunction after repetitive concussion, with associated functional benefit. By concurrently improving perfusion, oxygen delivery, intracranial compliance, and lymphatic drainage, PBM represents a mechanistically grounded, noninvasive candidate therapy for early adjunct intervention after mTBI.