Single-Exposure Prophylactic Transcranial Nano-Pulsed Laser Therapy Promotes Functional Resilience Following Mild...

Blast-induced traumatic brain injury is a prevalent and underreported condition, particularly among military service members, for whom effective prophylactic interventions are lacking. Nano-pulsed laser therapy (NPLT) is a non-invasive neuromodulatory approach that delivers short pulses of near-infrared light to generate optoacoustic effects within cerebral tissue and has previously demonstrated therapeutic benefit following TBI. In this study, we evaluated whether a single pre-exposure application of NPLT could confer protection against neurological, cognitive, and cellular sequelae of mild blast injury. Adult male Sprague-Dawley rats were randomized to receive NPLT or Sham treatment 24 h prior to either Sham or mild blast exposure using the Advanced Blast Simulator. Neurological reflexes and vestibulomotor function were assessed on post-injury days (PIDs) 1-5, while cognitive performance was evaluated using the Morris Water Maze on PIDs 13-17. Histological analyses of microglia, astrocytes, and myelination were performed on PID 17. A single mild blast did not significantly alter gross neurological function but was associated with deficits in fine motor coordination and cognitive performance. Pre-exposure NPLT modestly attenuated blast-associated fine motor dysfunction, with a significant improvement compared with TBI on PID 4. In the Morris Water Maze, TBI animals exhibited significantly increased latency compared with Sham on PIDs 13 and 17, whereas NPLT + TBI animals did not significantly differ from Sham across the testing period, consistent with preservation of cognitive performance. Histological responses were regionally heterogeneous: NPLT alone produced distinct glial alterations, while NPLT + TBI animals exhibited a mixture of treatment- and injury-associated responses rather than uniform normalization to uninjured controls. NPLT did not prevent localized blast-associated reductions in corpus callosum myelin staining. In naive animals, NPLT significantly increased hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression 24 h after treatment. A single pre-injury application of NPLT was associated with functional resilience following mild blast exposure despite persistent and regionally heterogeneous histopathological alterations. Increased hippocampal BDNF 24 h after NPLT, together with region-specific glial changes following NPLT in the absence of injury, demonstrates that a single treatment produces sustained molecular and cellular effects before blast exposure. These findings are consistent with the hypothesis that prophylactic NPLT establishes an altered pre-injury biological state that may modify the subsequent response to blast and support further investigation of NPLT as a prophylactic strategy and of the mechanisms underlying NPLT-associated preconditioning.