The mechanisms underlying the neuroprotection of XXMD against BBB disruption and ischemic injury induced by focal cerebral ischemia and reperfusion. Briefly, focal cerebral ischemia and reperfusion resulted in increase in MMP-9, MMP-2, and VEGF at the early stage of cerebral ischemia and reperfusion, which degraded the tight junction proteins or led to tight junction disassembly, further caused changes to the BBB ultrastructure and increased BBB permeability. Eventually, these alterations led to BBB disruption and ischemic injury, which includes cerebral infarction, neurological deficits, and brain edema. Interestingly, XXMD administration notably downregulated the expression levels of MMP-9, -2, and VEGF, further enhanced the tight junction and minimized BBB ultrastructure and permeability changes. As a result, XXMD administration inhibited BBB disruption and alleviated ischemic injury. The open scissors indicate the effects of XXMD treatment on cerebral injury following stroke and reperfusion.