2022-05-062022-05-062022https://hdl.handle.net/20.500.12503/30838Background: Branched-chain amino acids (BCAA) are known to be neurorestorative after traumatic brain injury (TBI). Despite clinically significant improvements in severe TBI patients given BCAA, the approach is largely an unrecognized option. Furthermore, TBI continues to be the most common cause of morbidity and mortality in adolescents and adults. In this study, we sought to demonstrate the neuroprotective and restorative effects of BCAA on the sequelae of TBI. No study has evaluated whether BCAA can be preventive or neuroprotective if taken before a TBI. We hypothesized that if BCAA were elevated in the circulation prior to TBI, the brain would readily access the BCAA and the severity of injury could be reduced. Methods: A standard weight-drop method was used on 50 adult mice to model a closed-head TBI in humans. The mice were randomized into groups that were shams, untreated, and pre-treated with BCAA, post-treated with BCAA, or pre-treated + post-treated with BCAA. Pretreated mice received BCAA through supplemented water and were dosed via oral gavage 45 mins prior to TBI induction. All mice underwent beam walking to assess motor recovery and Morris water maze assessed cognitive function post-injury. Results: Pre-treated and pre-treated + post-treated mice exhibited significantly better motor recovery and cognitive function than the other groups. The pre-treated + post-treated group performed the best overall while the post-treated group only improved in memory after day 7 of the study. Conclusion: This is the first study, animal or human, to demonstrate BCAA are neuroprotective and neurorestorative after TBI, most likely through the important roles of BCAA to glutamate homeostasis.enposter