• Hao Zhao, Yunjun Li, Lihua Chen, Chunsen Shen, Zongyu Xiao, Ruxiang Xu, Ji Wang, and Yongchun Luo.
• Department of Neurosurgery, The Seventh Medical Center of the PLA General Hospital, Beijing, 100000, China.
• Neuroscience. 2019 Oct 1; 417: 11-23.

AbstractEarly 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.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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