Ischemic stroke is the leading cause of human disability and mortality in the world. Neuroinflammation is the main pathological event following ischemia which contributes to secondary brain tissue damage and is driven by infiltration of circulating immune cells such as macrophages. Because of neuroprotective properties against ischemic brain damage, estrogens have the potential to become of therapeutic interest. However, the exact mechanisms of neuroprotection and signaling pathways is not completely understood. In the current study, 12-week-old male Wistar rats underwent an experimental ischemia by occluding the middle cerebral artery transiently (tMCAO) for 1 h. Male rats subjected to tMCAO were randomly assigned to receive 17β-estradiol or vehicle treatment. The animals were sacrificed 72 h post tMCAO, transcardially perfused and the brains were proceeded either for TTC staining and gene analysis or for flow cytometry (CD45, CD11b, CD11c, CD40). We found that 17β-estradiol substitution significantly reduced the cortical infarct which was paralleled by an improved Garcia test scoring. Flow cytometry revealed that CD45⁺ cells as well as CD45⁺CD11b⁺CD11c⁺ cells were massively increased in tMCAO animals and numbers were nearly restored to sham levels after 17β-estradiol treatment. Gene expression analysis showed a reperfusion time-dependent upregulation of the markers CD45, CD11b and the activation marker CD40. The reduction in gene expression after 72 h of reperfusion and simultaneous 17β-estradiol substitution did not reach statistical significance. These data indicate that 17β-estradiol alleviated the cerebral ischemia-reperfusion injury and selectively suppressed the activation of the neuroinflammatory cascade via reduction of the number of activated microglia or infiltrated monocyte-derived macrophages in brain.

缺血性中风是世界上人类残疾和死亡的主要原因。神经炎症是缺血后的主要病理事件，导致继发性脑组织损伤，并由巨噬细胞等循环免疫细胞的浸润驱动。由于雌激素具有针对缺血性脑损伤的神经保护特性，因此有可能具有治疗意义。然而，神经保护和信号通路的确切机制尚不完全清楚。在当前的研究中，12周大的雄性Wistar大鼠通过短暂闭塞大脑中动脉（tMCAO）1小时来进行实验性缺血。接受 tMCAO 的雄性大鼠被随机分配接受 17β-雌二醇或载体治疗。 tMCAO 后 72 小时处死动物，经心脏灌注，并对大脑进行 TTC 染色和基因分析或流式细胞术（CD45、CD11b、CD11c、CD40）。我们发现 17β-雌二醇替代显着减少了皮质梗塞，同时加西亚测试评分也得到了改善。流式细胞术显示，tMCAO 动物中 CD45 ⁺细胞以及 CD45 ⁺ CD11b ⁺ CD11c ⁺细胞大量增加，并且在 17β-雌二醇治疗后数量几乎恢复到假手术水平。基因表达分析显示标记物 CD45、CD11b 和激活标记物 CD40 存在再灌注时间依赖性上调。再灌注72小时和同时17β-雌二醇替代后基因表达的减少没有达到统计学显着性。 这些数据表明，17β-雌二醇减轻了脑缺血再灌注损伤，并通过减少脑中活化的小胶质细胞或浸润的单核细胞衍生巨噬细胞的数量来选择性抑制神经炎症级联的激活。