Neural stem cell–derived exosomes regulate cell proliferation,migration, and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

Background : Our previous study found that mouse embryonic neural stem cell(NSC)–derived exosomes(EXOs) regulated NSC differentiation via the miR-9/Hes1axis. However, the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR-9/Hes1 axis.Methods : Immunofluorescence, quantitative real-time polymerase chain reaction, cell counting kit-8 assay, wound healing assay, calcein-acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results : EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR-9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR-9downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-i nduced mice. Meanwhile, EXO treatment improved cerebrovascular alterations.Conclusion : NSC-derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore, EXO therapeutic strategies could be considered for hypoxia-i nduced vascular injury.