In conclusion, the present study demonstrates that n-EMVs and OGD-EMVs have opposite effects on regulating astrocyte activities and BBB integrity via regulating the PI3K/AKT and Caspase-9/Bcl-2 signal pathways and that n-EMVs and OGD-EMVs have differently impacts CBF and cerebral ischemic damage, which could offer novel therapeutic strategies for ischemic stroke and BBB disruption related diseases. Here, CASP9 is linked to ischemic stroke.