The role of metalloproteinases on blood-brain barrier breakdown after ischemic stroke

Abstract

The role of the blood-brain barrier (BBB) is to preserve the neuronal microenvironment, which is essential for the normal function of the brain. As a functional entity, BBB includes several cell types and the extracellular matrix (ECM). Microvascular endothelial cells coupled by tight junctions and featuring only a very few endocytotic vesicles are responsible for the permeability properties of the BBB [1]. Although in discontinuous contact with endothelial cells through their end feet, astrocytes seem also to actively participate in BBB phenotype [2]. Similarly, pericytes have been shown to change endothelial behavior [3–5>]. Finally, the endothelial basal lamina represents the non-cellular component of BBB. Produced by endothelial cells, the basal lamina is a specialized ECM composed of type IV collagen, fibronectin, laminin and various proteoglycans [6]. The ECM components are connected to endothelial cells via integrins and may regulate distinct biological events such as cellular differentiation, survival, morphology, adhesion and gene expression [7–10]. When BBB integrity is lost, inflammatory cells and fluid penetrate the brain, causing vasogenic edema and cell death [11, 12]. BBB permeability properties are challenged in various brain pathologies including ischemic stroke and several mechanisms of BBB disruption have been considered, involving bradykinin [13] other proinflammatory mediators [14] and oxygen free radicals [15, 16>].KeywordsMiddle Cerebral Artery OcclusionFocal Cerebral IschemiaVasogenic EdemaCereb Blood FlowSecondary Brain InjuryThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.