Subarachnoid hemorrhage (SAH) triggers severe neuroinflammation and cognitive impairment, where microglial M1 polarization exacerbates the injury and M2 polarization mitigates damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), carrying microRNA (miR)-140-5p, offer therapeutic promise by targeting the cAMP/PKA/CREB pathway and modulating microglial responses, demonstrating a novel approach for addressing SAH-induced brain injury. This research explored the role of miR-140-5p delivered by MSC-EVs in mitigating brain damage following SAH. Serum from SAH patients and healthy individuals was analyzed for miR-140-5p and cAMP levels. The association between miR-140-5p levels, brain injury severity, and patient survival was examined, along with the target relationship between miR-140-5p and histone deacetylases 7 (HDAC7). MSC-EVs were characterized for their ability to cross the blood-brain barrier and modulate the HDAC7/AKAP12/cAMP/PKA/CREB axis, reducing M1 polarization and inflammation. The therapeutic effect of MSC-EV-miR-140-5p was demonstrated in an SAH mouse model, showing reduced neuronal apoptosis and improved neurological function. This study highlights the potential of MSC-EV-miR-140-5p in mitigating SAH-induced neuroinflammation and brain injury, providing a foundation for developing MSC-EV-based treatments for SAH.

蛛网膜下腔出血 (SAH) 会引发严重的神经炎症和认知障碍，其中小胶质细胞 M1 极化会加剧损伤，而 M2 极化会减轻损伤。携带 microRNA (miR)-140-5p 的间充质干细胞来源的细胞外囊泡 (MSC-EV) 通过靶向 cAMP/PKA/CREB ​​通路和调节小胶质细胞反应提供治疗前景，展示了一种解决 SAH 诱导的大脑的新方法受伤。这项研究探讨了 MSC-EV 传递的 miR-140-5p 在减轻 SAH 后脑损伤中的作用。分析 SAH 患者和健康个体的血清中 miR-140-5p 和 cAMP 水平。检查了 miR-140-5p 水平、脑损伤严重程度和患者生存之间的关联，以及 miR-140-5p 和组蛋白脱乙酰酶 7 (HDAC7) 之间的目标关系。 MSC-EV 的特点是能够穿过血脑屏障并调节 HDAC7/AKAP12/cAMP/PKA/CREB ​​轴，从而减少 M1 极化和炎症。 MSC-EV-miR-140-5p 的治疗效果在 SAH 小鼠模型中得到证实，显示神经元凋亡减少并改善神经功能。这项研究强调了 MSC-EV-miR-140-5p 在减轻 SAH 诱导的神经炎症和脑损伤方面的潜力，为开发基于 MSC-EV 的 SAH 治疗方法奠定了基础。