Therefore, in this study, we tested the hypothesis on an in vivo model of middle cerebral artery occlusion (MCAO) and an in vitro model of oxygen glucose deprivation (OGD) that cerebral ischemia induces β2-AR activation, and activated β2-AR upregulates HIF-1α to promote MMP-2 secretion and BBB disruption. Here, HIF1A is linked to Cerebral ischemia.