Ischemic stroke is typified by hypoxia and a cascade of pathophysiological events, including metabolic dysfunction, ionic dysregulation, excitotoxicity, inflammatory infiltration, and oxidative stress. These ultimately result in neuronal apoptosis or necrosis with constrained neuroregenerative capabilities. In this study, neural stem cells (NSCs) under conditions of oxygen–glucose deprivation (OGD) in vitro and following middle cerebral artery occlusion (MCAO) in vivo were explored. Transcriptome sequencing revealed a decline in NSC differentiation and neurogenesis after OGD exposure, which was related to cellular senescence. This observation was corroborated by increased senescence markers in the MCAO mouse model, reduction in NSC numbers, and decline in neurogenesis. Importantly, iMSC-sEVs (induced mesenchymal stem cells-small extracellular vesicles) have the therapeutic potential to alleviate NSC senescence and rejuvenate their regenerative capacities both in vitro and in vivo. Moreover, iMSC-sEVs contribute to the recovery of cognitive function and synapse loss caused by MCAO.

缺血性中风的典型特征是缺氧和一系列病理生理事件，包括代谢功能障碍、离子失调、兴奋性毒性、炎症浸润和氧化应激。这些最终导致神经元凋亡或坏死，神经再生能力受到限制。在这项研究中，探索了体外氧糖剥夺（OGD）条件下和体内大脑中动脉闭塞（MCAO）条件下的神经干细胞（NSC）。转录组测序揭示了 OGD 暴露后 NSC 分化和神经发生的下降，这与细胞衰老有关。MCAO 小鼠模型中衰老标志物的增加、NSC 数量的减少和神经发生的下降证实了这一观察结果。重要的是，iMSC-sEV（诱导间充质干细胞 - 小细胞外囊泡）具有减轻 NSC 衰老并恢复其体外和体内再生能力的治疗潜力。此外，iMSC-sEV 有助于恢复由 MCAO 引起的认知功能和突触损失。