In the current study, we utilized in-vitro OGD insulted brain endothelial cells and neurons together with an in-vivo tMCAo mice model to demonstrate that BMSC-sEVs treatment effectively restored tight junction protein ZO-1 and Occludin expression levels together with protecting the injured neurons after cerebral ischemia, which contributed to the long-term neurological function amelioration in tMCAo mice. Here, OCLN is linked to brain ischemia.