Tu Li, Yang Xiu-Lin, Zhang Qian, Wang Qian, Tian Tian, Liu Dan, Qu Xiang, Tian Jin-Yong
a Department of Emergency , The Affiliated Hospital of Guizhou Medical University , Guizhou , China.
b Department of Emergency , Guizhou Provincial People's Hospital , Guizhou , China.
Neurol Res. 2018 Aug;40(8):702-708. doi: 10.1080/01616412.2018.1463900. Epub 2018 Apr 24.
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.
目的 早期脑损伤（EBI）被认为是蛛网膜下腔出血（SAH）患者预后不良的主要原因之一。贝沙罗汀是视黄酸X受体的激动剂，在中枢神经系统疾病中发挥保护作用。然而，贝沙罗汀在SAH中的确切作用尚未见报道。因此，本研究旨在确定给予贝沙罗汀是否能减轻SAH后小鼠的EBI，并探讨其潜在机制。方法 通过血管内穿刺在C57BL/6小鼠中诱导SAH。腹腔注射贝沙罗汀。在SAH后24小时检测神经功能评分、细胞死亡、小胶质细胞活化和促炎细胞因子。通过蛋白质印迹法测量PPARγ的表达。结果 结果显示，贝沙罗汀显著改善了SAH后的神经功能评分。此外，给予贝沙罗汀可显著减少细胞死亡数量和活化的小胶质细胞。与给予溶剂的小鼠相比，给予贝沙罗汀的小鼠在SAH后促炎细胞因子减少。与给予溶剂的对照组相比，贝沙罗汀治疗使PPARγ的表达显著增加。讨论 本研究表明，给予贝沙罗汀可保护SAH后的EBI，抑制细胞死亡，减轻小胶质细胞活化，并减轻神经炎症。其潜在机制可能部分涉及PPARγ的激活。
