β-carotene provides neuro protection after experimental traumatic brain injury via the Nrf2-ARE pathway.

We investigate whether beta-carotene, a known natural antioxidant, can reduce oxidative stress induced by traumatic brain injury. In addition, we investigated the underlying mechanism of traumatic brain injury focusing on the NF-E2-related factor (Nrf2) pathway. A controlled cortical impact model was used to mimic traumatic brain injury. Using this model, we evaluated brain edema, lesion volume, neurologic deficits, reactive oxygen species, and the expression of Nrf2-related protein markers. The results of our study demonstrated that cognitive performance and neural functions were improved with beta-carotene administration. In addition, beta-carotene reduced brain edema and reactive oxygen species levels after traumatic brain injury. Nrf2 nuclear accumulation was increased and was accompanied by decreased Keap1 expression. The expression of quinone oxidoreductase 1, a target gene of the Nrf2 signaling pathway was increased. However, lesion volume was not significantly reduced after beta-carotene treatment. Taken together, our data demonstrated that beta-carotene administration was neuroprotective and alleviated oxidative stress by modulating the Nrf2/Keap1-mediated antioxidant pathway in the traumatic brain injury model.