Exosomes and microRNAs (miRs) are critical in reducing ischemia/reperfusion (I/R) injury, but the mechanism of astrocyte-derived exosome (ATC-Exo)-transported miR-34c in cerebral I/R injury is unclear. A rat model of cerebral I/R injury was established in this study, and the rats were injected with ATC-Exos. An oxygen glucose deprivation/reperfusion (OGD/R) model in N2a cells was utilized to mimic cerebral I/R injury in vitro, and the effects of ATC-Exo-transported miR-34c on the biological episodes of OGD/R-stimulated N2a cells were evaluated. The downstream gene and pathway of miR-34c were verified, and a rescue experiment of the pathway was performed. Consequently, we found that I/R damaged neurons, and ATC-Exo-transported miR-34c alleviated the neuronal injury caused by I/R. In addition, ATC-Exo-transported miR-34c promoted proliferation and inhibited apoptosis in OGD/R-stimulated N2a cells. miR-34c targeted Toll-like receptor 7 (TLR7) and downregulated the NF-κB/MAPK axis. Treatment with NF-κB- or MAPK-specific inhibitors partially restored the impaired protection against I/R that was caused by ATC-Exos with low expression of miR-34c. Overall, ATC-Exo-transported miR-34c targets TLR7 to downregulate the NF-κB/MAPK axis and relieve neurological damage induced by I/R. This study may offer novel insight for the treatment of cerebral I/R injury.

外泌体和 microRNA (miR) 在减少缺血/再灌注 (I/R) 损伤方面至关重要，但星形胶质细胞衍生的外泌体 (ATC-Exo) 转运的 miR-34c 在脑 I/R 损伤中的机制尚不清楚。本研究建立大鼠脑 I/R 损伤模型，并注射 ATC-Exos。利用 N2a 细胞中的氧葡萄糖剥夺/再灌注 (OGD/R) 模型来模拟体外脑 I/R 损伤，并评估了 ATC-Exo 转运的 miR-34c 对 OGD/R 刺激的 N2a 细胞生物学事件的影响。验证了miR-34c的下游基因和通路，并进行了该通路的拯救实验。因此，我们发现 I/R 损伤神经元，ATC-Exo 转运的 miR-34c 减轻了 I/R 引起的神经元损伤。此外，ATC-Exo 转运的 miR-34c 促进了 OGD/R 刺激的 N2a 细胞的增殖并抑制了细胞凋亡。miR-34c 靶向 Toll 样受体 7 (TLR7) 并下调 NF-κB/MAPK 轴。用 NF-κB 或 MAPK 特异性抑制剂治疗部分恢复了对 I/R 的保护受损，这是由 miR-34c 低表达的 ATC-Exos 引起的。总体，ATC-Exo 转运的 miR-34c 靶向 TLR7 以下调 NF-κB/MAPK 轴并缓解 I/R 诱导的神经损伤。这项研究可能为脑 I/R 损伤的治疗提供新的见解。