Abstract TP103: Photobiomodulation Improves Neurovascular Function and Minimizes Brain Injury Outcome in Traumatic Brain Injury Mice

Background: Traumatic brain injury (TBI) initiates a complex secondary injury cascade, including breakdown of the blood-brain barrier (BBB), neuroinflammation, and impaired neurovascular coupling (NVC)—the crucial process that matches cerebral blood flow to neuronal activity. These pathologies contribute to persistent cognitive dysfunction. Photobiomodulation (PBM), a non-invasive therapy using near-infrared light, has shown neuroprotective effects, but its specific impact on the neurovascular unit after TBI remains unclear. Objective: This study aimed to test the hypothesis that PBM therapy alleviates TBI-induced cognitive deficits by mitigating BBB permeability and restoring functional NVC in a mouse model. Methods: Adult C57BL/6 mice were subjected to a moderate controlled cortical impact (CCI) injury. Twenty-four hours post-injury, mice began daily transcranial PBM treatment (808 nm) or sham treatment for four weeks. Cognitive and motor function were assessed using behavioral tests, while biochemical and histological analyses were conducted to evaluate BBB integrity and protein expression related to tight junction proteins (TJs). NVC function was assessed by measuring cerebral blood flow changes. Results: We found that CCI significantly induced BBB leakage, impaired cerebral microcirculation, lead to profound deficits in motor function, spatial learning and memory. PBM treatment significantly alleviated lesion size and promoted learning, motor, and memory recovery in TBI mice. Besides, PBM treatment also enhanced BBB integrity by upregulating the TJs, restored a robust neurovascular response by elevating cerebral blood flow, and markedly decreased Iba1 induced neuroinflammatory response as well. Conclusion: These findings demonstrates that PBM effectively targets the neurovascular unit to ameliorate key TBI pathologies, by enhancing BBB integrity and restoring NVC, PBM represents a promising therapeutic strategy to mitigate secondary injury and improve long-term cognitive outcomes after TBI.