Background. In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes on the BBB after SAH. Methods. The SAH model was established by perforating the blood vessels. BMSCs were transfected with TSG-6 inhibitor plasmid and cocultured with astrocytes. Intravenous transplantation of BMSCs was utilized to treat SAH rats. We performed ELISA, neurological scoring, Evans blue staining, NO measurement, immunofluorescence, BBB permeability, Western blot, HE staining, Nissl staining, and immunohistochemistry to evaluate the effect of BMSCs on astrocytes and BBB. Results. SAH rats showed BBB injury, increased BBB permeability, and brain histological damage. BMSCs will secrete TSG-6 after being activated by TNF-α. Under the influence of TSG-6, the NF-κB and MAPK signaling pathways of astrocytes were inhibited. The expression of iNOS was reduced, while occludin, claudin 3, and ZO-1 expression was increased. The production of harmful substances NO and ONOO^- decreased. The level of inflammatory factors decreased. The apoptosis of astrocytes was weakened. TSG-6 secreted by BMSCs can relieve inflammation caused by SAH injury. The increase in BBB permeability of SAH rats was further reduced and the risk of rebleeding was reduced. Conclusion. BMSCs can regulate the activation of astrocytes through secreting TSG-6 in vivo and in vitro to protect BBB.

中文翻译：

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BMSCs通过TSG-6调控星形胶质细胞保护蛛网膜下腔出血后的血脑屏障

背景。在蛛网膜下腔出血 (SAH) 患者中，血脑屏障 (BBB) 的损伤可能会危及生命。间充质干细胞因其多效性而被广泛用于临床研究。本研究旨在探讨 BMSCs 调节星形胶质细胞对 SAH 后 BBB 的影响。方法。SAH模型是通过对血管进行穿孔建立的。用 TSG-6 抑制剂质粒转染 BMSCs 并与星形胶质细胞共培养。BMSCs的静脉内移植用于治疗SAH大鼠。我们进行了 ELISA、神经学评分、埃文斯蓝染色、NO 测量、免疫荧光、BBB 通透性、蛋白质印迹、HE 染色、Nissl 染色和免疫组织化学，以评估 BMSCs 对星形胶质细胞和 BBB 的影响。结果。SAH 大鼠表现出 BBB 损伤、BBB 通透性增加和脑组织学损伤。BMSCs 被 TNF- α激活后会分泌 TSG-6 。在TSG-6的影响下，星形胶质细胞的NF-κB和MAPK信号通路受到抑制。iNOS 的表达减少，而 occludin、claudin 3 和 ZO-1 的表达增加。有害物质 NO 和 ONOO ^-的产生减少。炎症因子水平下降。星形胶质细胞的凋亡减弱。BMSCs分泌的TSG-6可以缓解SAH损伤引起的炎症。SAH大鼠血脑屏障通透性增加进一步降低，再出血风险降低。结论. BMSCs可以通过在体内和体外分泌TSG-6来调节星形胶质细胞的活化，从而保护BBB。