Blood-brain barrier tight junction permeability and ischemic stroke

• Published in: Neurobiology of disease Vol. 32; no. 2; pp. 200 - 219
• Main Authors: Sandoval, Karin E, Witt, Ken A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2008; Elsevier
• Subjects: Angiogenesis; Animals; Biphasic; Blood-brain barrier; Blood-Brain Barrier - physiopathology; Edema; Humans; Ischemia; Neurology; Neurovascular-unit; Permeability; Phasic; Reperfusion; Stroke; Stroke - pathology; Stroke - physiopathology; Stroke-bed algorithm; Tight junction; Tight Junctions - metabolism; Edema; Angiogenesis; Stroke; Reperfusion; Ischemia; Blood-brain barrier; Neurovascular-unit; Stroke-bed algorithm; Tight junction; Biphasic; Phasic
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2008.08.005

Abstract The blood-brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels, providing a dynamic interface between the peripheral circulation and the central nervous system. The tight junctions (TJs) between the endothelial cells serve to restrict blood-borne substances from entering the brain. Under ischemic stroke conditions decreased BBB TJ integrity results in increased paracellular permeability, directly contributing to cerebral vasogenic edema, hemorrhagic transformation, and increased mortality. This loss of TJ integrity occurs in a phasic manner, which is contingent on several interdependent mechanisms (ionic dysregulation, inflammation, oxidative and nitrosative stress, enzymatic activity, and angiogenesis). Understanding the inter-relation of these mechanisms is critical for the development of new therapies. This review focuses on those aspects of ischemic stroke impacting BBB TJ integrity and the principle regulatory pathways, respective to the phases of paracellular permeability.