Inhibition of MAPT enhances the effect of bexarotene and attenuates the damage after traumatic brain injury using in vivo and in vitro experiments.

Traumatic brain injury (TBI) is the leading cause of death and disability around the world in all age groups. The primary injury of TBI is exacerbated by secondary injury, leading to an increased inflammatory response, cell death and even impairment of neurological function. Bexarotene has been found to improve neurological function in mice in an ApoE-dependent manner, but the detailed mechanism is not fully clear. Upregulated expression of MAPT has been found in mouse models after TBI; therefore, we hypothesized that inhibition of MAPT might contribute to the effects of bexarotene treatment in TBI models. Herein, we found that inhibition of MAPT enhanced the effects of bexarotene in increasing cellular viability and restoring brain function, and expression of anti-oxidative and anti-apoptotic molecules were elevated in response to inhibition of MAPT. These effects might be mediated by activation of the Nrf2/HO-1 signalling pathway and inhibition of the MAPK/NF-kB signalling pathway. Thus, we concluded that inhibition of MAPT might represent a novel treatment target for TBI.