title: Advances in the vascular pathophysiology of ischemic stroke.
abstract: The cerebral vascular supply is constructed to protect the cerebral hemispheres and brainstem from the consequences of blood flow cessation. Reversal of blood flow around local obstructions is a feature of the microvascular beds of the striatum and cerebral cortex. Cerebral capillaries of these beds consist of endothelial cells, basal lamina, and astrocyte end-feet that sit in close apposition. The interaction of astrocytes with neurons indicates the close relationship of microvessels to neurons. These relationships are altered when blood flow ceases in the supplying artery. Increased endothelial cell permeability and endocytoses lead to edema formation, and matrix degradation is associated with hemorrhage. Autoregulation is lost. Ischemia initiates leukocyte adhesion receptor expression, which is promoted by cytokine generation from the neuropil and activated monocytes. "Preactivation" may further augment the inflammatory responses to ischemia. The activation of cerebral microvessels by ischemia is heterogeneous, involving alterations in integrin-matrix interactions, leukocyte-endothelial cell adhesion, permeability changes, and the "no-reflow" phenomenon due to platelet activation, fibrin formation, and leukocyte adhesion. Ischemia produces swelling of the microvascular endothelium, and rapid detachment and swelling of the astrocyte end-feet. Ischemic injury targets the microvasculature, where the inflammatory responses are initiated and contribute to tissue injury.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. grgdlzop@hermes.scripps.edu
authors.forename: G J
authors.initials: GJ
authors.lastname: del Zoppo
authors.forename: J M
authors.initials: JM
authors.lastname: Hallenbeck
mesh_terms: D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008833:Microcirculation / Q000502:physiology; D020521:Stroke / Q000209:etiology / Q000503:physiopathology*