Bexarotene attenuates early brain injury via inhibiting micoglia activation through PPARγ after experimental subarachnoid hemorrhage.

Objectives Early brain injury (EBI) is considered to be one of the main causes of poor outcome in subarachnoid hemorrhage (SAH) patients. Bexarotene is an agonist of retinoid X receptor and plays a protective role in central nervous system diseases. However, the exact role of bexarotene in SAH has not been reported. Therefore, the present study was to determine whether bexarotene administration attenuate EBI after SAH in mice and to explore the underlying mechanism. Methods SAH was induced in C57BL/6 mice by endovascular perforation. Bexarotene was administrated intraperitoneally. Neurological score, cell death, microglia activation, and pro-inflammatory cytokines were detected at 24 h after SAH. The expression of PPARγ was measured by Western blot. Results Results showed that bexarotene significantly improved neurological score after SAH. In addition, the number of cell death and activated microglia were significantly reduced by bexarotene administration. Compared with vehicle-treated mice, bexarotene-treated mice showed reduced pro-inflammatory cytokines after SAH. The expression of PPARγ was significantly increased with bexarotene treatment compared with vehicle-treated controls. Discussion The present study demonstrats that bexarotene administration protects against EBI after SAH, inhibiting cell death, attenuating microglia activation, and alleviating neuroinflammation. The underlying mechanism may partially involve the activation of PPARγ.