Seifert Hilary A, Benedek Gil, Liang Jian, Nguyen Ha, Kent Gail, Vandenbark Arthur A, Saugstad Julie A, Offner Halina
Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
Cell Immunol. 2017 Aug;318:49-54. doi: 10.1016/j.cellimm.2017.06.003. Epub 2017 Jun 8.
Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19CD5CD1d B10 cells as well as anti-inflammatory CD11bCD206 microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60min middle cerebral artery occlusion followed by 96h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females.
中风是美国导致残疾的主要原因。性别差异,包括女性梗死灶较小以及男性免疫介导的炎症参与程度较高,可能会影响免疫调节干预措施的疗效。为了研究这些差异,我们试图在雌性和雄性小鼠中确定不同的中风改善机制。当前研究表明,在经历60分钟大脑中动脉闭塞并再灌注96小时的雌性小鼠而非雄性小鼠中,同侧半球与对侧半球相比,梗死灶较小,调节性CD19CD5CD1d B10细胞水平升高,以及抗炎性CD11bCD206小胶质细胞/巨噬细胞增多。此外,患有大脑中动脉闭塞的雌性小鼠脾脏总细胞数增加,但脾脏中B10水平较低。这些结果阐明了不同的性别依赖性调节机制,这些机制解释了女性中风严重程度降低的原因,并强调了在雄性和雌性中都需要测试中风免疫调节疗法的必要性。