Inflammatory responses play a major role in the pathophysiology of cerebral ischemia. Mesenchymal stem cell-derived exosomes (MSC-exos) have important anti-inflammatory effects on the treatment of organ injury. This study aimed to determine the anti-inflammatory effect and furtherly investigate the potential mechanism of MSC-exos on acute cerebral ischemia. MSC-exos were isolated by ultracentrifugation, characterized by transmission electron microscopy and FACS. Rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) surgery were administered MSC-exos through the tail vein. In vitro, microglia exposed to oxygen- and glucose-deprivation (OGD) and leukotrienes were used to study the protective mechanism of exosomes against ischemia/reperfusion-induced inflammation. The intake of exosomes into microglia was visualized through immunofluorescence staining. The results showed that MSC-exos treatment significantly improved motor, learning and memory abilities of MCAO/R rats 7 days later. The production of pro-inflammatory factors decreased, while the anti-inflammatory cytokines and neurotrophic factors increased both in the cortex and hippocampus of ischemic hemisphere as well as in the culture supernatant of microglia treated with OGD and NMLTC4. MSC-exos treatment also significantly inhibited M1 microglia polarization and increased M2 microglia cells. Furthermore, western blot analysis demonstrated that CysLT2R expression and ERK1/2 phosphorylation were downregulated both in vivo and in vitro. Thus, MSC-exos attenuated brain injury and inhibited microglial inflammation by reversing CysLT2R-ERK1/2 mediated microglia M1 polarization.

中文翻译：

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MSCs衍生的外来体通过逆转CysLT2R-ERK1 / 2介导的小胶质细胞M1极化来减轻急性脑损伤并抑制小胶质细胞炎症。

炎症反应在脑缺血的病理生理中起主要作用。间充质干细胞来源的外来体（MSC-exos）对器官损伤的治疗具有重要的抗炎作用。这项研究旨在确定抗炎作用，并进一步研究MSC-exos对急性脑缺血的潜在机制。通过超速离心分离MSC-exos，其特征在于透射电子显微镜和FACS。大脑中动脉闭塞/再灌注（MCAO / R）手术的大鼠通过尾静脉给予MSC-exos。在体外，暴露于缺氧和葡萄糖剥夺（OGD）和白三烯的小胶质细胞用于研究外泌体对缺血/再灌注诱导的炎症的保护机制。通过免疫荧光染色观察外泌体进入小胶质细胞的情况。结果表明，MSC-exos治疗在7天后显着改善了MCAO / R大鼠的运动，学习和记忆能力。缺血半球的皮质和海马以及用OGD和NMLTC4处理的小胶质细胞培养上清液中促炎因子的产生减少，而抗炎细胞因子和神经营养因子增加。MSC-exos处理还显着抑制M1小胶质细胞极化并增加M2小胶质细胞。此外，蛋白质印迹分析表明CysLT2R表达和ERK1 / 2磷酸化在体内和体外均被下调。从而，