Mechanisms of Endothelial Injury and Blood-Brain Barrier Dysfunction in Stroke

The blood-brain barrier (BBB) regulates CNS homeostasis and is the most significant obstacle to effective brain drug delivery. It possesses characteristics (i.e., tight junction protein complexes, influx and efflux transporters) that control permeation of circulating solutes including therapeutic agents. Ischemic stroke can cause injury to the brain microvascular endothelium at both the structural and functional level, which leads to considerable BBB dysfunction and significant CNS pathology. Several pathophysiological mechanisms (i.e., oxidative stress, inflammation) have been identified that can mediate BBB dysfunction during ischemic stroke. This chapter summarizes current knowledge in this area and highlights novel pharmacological approaches that can be utilized for protection against injury to brain microvascular endothelial cells in the setting of stroke.