Blood-Brain Barrier Integrity and Glial Support: Mechanisms that can be Targeted for Novel Therapeutic Approaches in Stroke

摘要: The blood-brain barrier (BBB) is a critical regulator of brain homeostasis. Additionally, the BBB most significant obstacle to effective CNS drug delivery. It possesses specific charcteristics (i.e., tight junction protein complexes, influx and efflux transporters) that control permeation circulating solutes including therapeutic agents. In order form this "barrier," microvascular endothelial cells require support adjacent astrocytes microglia. This intricate relationship also occurs between other cell types structures pericytes, neurons, extracellular matrix), which implies existence "neurovascular unit." Ischemic stroke can disrupt neurovascular unit at both structural functional level, leads an increase in leak across BBB. Recent studies have identified several pathophysiological mechanisms oxidative stress, activation cytokine-mediated intracellular signaling systems) mediate changes during ischemic stroke. review summarizes current knowledge area emphasizes pathways signaling, glial-expressed receptors/targets) be manipulated pharmacologically for i) preservation glial integrity ii) and/or transport Targeting these present novel opportunity optimization delivery therapeutics setting