Physiological Effects of Photobiomodulation Therapy in the Treatment of Multiple Concussions

Repeated concussion traumatic brain injury (TBI) results in long-term brain damage and cognitive dysfunctions, leading to neurodegenerative diseases. The brain clearance system plays a crucial role in TBI recovery and neurodegenerative disease amelioration by draining waste macromolecules from the brain. Pharmacological therapeutics have failed to demonstrate benefits in human TBI. Photobiomodulation (PBM) has gained interest in neuroscience and has been shown to improve brain drainage. Here, we evaluated the efficiency of PBM in the treatment of multiple concussions in mice and the augmentation of the brain clearance system. Three consecutive closed-head concussive TBIs were induced with a 1-h interval to the left hemisphere in C57BL/6 male mice. A near-infrared irradiation (1270 nm, 10 mW/cm²) was used for PBM 4 h after the last TBI and the following 3 days twice a day. Laser speckle contrast imaging was used to assess cerebral blood flow (rCBF). In vivo 2-photon laser scanning microscopy assessed PBM effects on cerebral microcirculation, tissue oxygen supply (NADH), and meningeal lymphatics clearance. Brain compliance was evaluated by intracranial pressure waveform analysis. Neurological severity scores were obtained at 0-3 days after TBI. Two-way ANOVA for multiple comparisons was used to test intergroup differences, with the statistical significance set at p < 0.05. Multiple concussions progressively impaired rCBF, cortical microcirculation, tissue oxygen supply, and brain drainage function (p < 0.05). Compared to the sham-treated group, PBM improved rCBF, microcirculation, tissue oxygenation, and the brain drainage system (p < 0.05). Neurological function was more preserved in the PBMT group than in sham-treated mice (p < 0.05). Our study demonstrated that PBMT can be used as an adjunct therapy even in the acute period of TBI.