HucMSCs-Derived miR-206-Knockdown Exosomes Contribute to Neuroprotection in Subarachnoid Hemorrhage Induced Early Brain Injury by Targeting BDNF

Abstract

Early brain injury (EBI) is the most important potentially treatable cause of mortality and morbidity following subarachnoid hemorrhage (SAH). Apoptosis is one of the main pathologies of SAH-induced EBI. Numerous studies suggest that human umbilical cord derived mesenchymal stem cells (hucMSCs) may exert neuroprotective effect through exosomes instead of transdifferentiation. In addition, microRNA-206 (miR-206) targets BDNF and plays a critical role in brain injury diseases. However, the therapy effect of miR-206 modified exosomes on EBI after SAH and its regulatory mechanism have not been elucidated. Here, to identify whether hucMSCs-derived miR-206-knockdown exosomes have a better neuroprotective effect, we established SAH rat model and treated it with the exosomes to research the mechanism of miR-206 in EBI after SAH. We found that treatment with hucMSCs-derived miR-206-knockdown exosomes has a greater neuroprotective effect on SAH-induced EBI compared to treatment with simple exosomes. The miR-206-knockdown exosomes could significantly improve neurological deficit and brain edema and suppress neuronal apoptosis by targeting BDNF. Moreover, the BDNF/TrkB/CREB pathway was activated following treatment with miR-206 modified exosomes in vivo. In summary, these findings indicate that the hucMSCs-derived miR-206-knockdown exosomes prevent early brain injury by inhibiting apoptosis via BDNF/TrkB/CREB signaling. This may serve as a novel therapeutic target for treatment of SAH-induced EBI.