Astrocyte-derived exosome-transported microRNA-34c is neuroprotective against cerebral ischemia/reperfusion injury via TLR7 and the NF-κB/MAPK pathways.

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.