Blood-brain barrier (BBB) is composed of highly specialized cerebrovascular endothelial cells, seals brain tissue from the circulating blood, and prevents blood, bacteria or toxins from reaching the central nervous system (CNS). In acute ischemic stroke, BBB is disrupted, and blood solutes penetrate into the CNS parenchymal extracellular space then cause cerebral edema. Enrichment of mitochondria in the BBB capillaries has been observed 3 decades ago. It has been recognized that mitochondria involve in maintaining of ion differentials and transportation of chemicals between blood and brain extracellular fluid. Mitochondria are crucial for shaping the cerebral endothelial capillary architecture and the integrity of the BBB . Mitochondrial blockade rapidly opens the BBB both in vitro cell culture model and in vivo epidural application model, increases BBB permeability, and exacerbates stroke outcomes.