To date, the neuroprotective effects of statins on intracerebral hemorrhage (ICH) are not well established. This study explored the effect and potential mechanism of simvastatin treatment on ICH. In the present study, the effects of simvastatin on hematoma absorption, neurological outcome, CD36 expression and microglia polarization were examined in rat model of ICH model. In the meantime, inhibitory effect of PPARy inhibitor GW9662 was investigated following ICH. Additionally, the effect of simvastatin on PPARy activation was also investigated in rat ICH model and primary microglia culture. Much more, the role of PPARy and CD36 in simvastatin-mediated erythrocyte phagocytosis was also detected by using in vivo or in vitro phagocytosis models, respectively. After ICH, simvastatin promoted hematoma absorption and improved neurological outcome after ICH while upregulating CD36 expression and facilitating M2 phenotype polarization in perihematomal microglia. In addition, simvastatin increased PPARy activation and reinforced microglia-induced erythrocyte phagocytosis in vivo and in vitro. All above effects of simvastatin were abolished by PPARy inhibitor GW9662. In conclusion, our data suggested that simvastatin could enhance hematoma clearance and attenuate neurological deficits possibly by activating PPARy. (C) 2017 Elsevier Ltd. All rights reserved.
基金：
Grant Nos. 81771241 (Z.C) from the
National Natural Science Foundation of China and Grant No.
2014CB541606 (H.F. and G.Z.) from the National Key Basic Research
Development Program of China.
第一作者机构：[1]Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, 30 Gaotanyan St, Chongqing 400038, Peoples R China
通讯作者：
通讯机构：[1]Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, 30 Gaotanyan St, Chongqing 400038, Peoples R China[*1]Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China
推荐引用方式(GB/T 7714)：
Wang Yuelong,Chen Qianwei,Tan Qiang,et al.Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPAR gamma-dependent manner[J].NEUROPHARMACOLOGY.2018,128:244-254.doi:10.1016/j.neuropharm.2017.10.021.
APA：
Wang, Yuelong,Chen, Qianwei,Tan, Qiang,Feng, Zhou,He, Zhenlin...&Chen, Zhi.(2018).Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPAR gamma-dependent manner.NEUROPHARMACOLOGY,128,
MLA：
Wang, Yuelong,et al."Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPAR gamma-dependent manner".NEUROPHARMACOLOGY 128.(2018):244-254
医学