Microvascular responses to cerebral ischemia/inflammation.
Experimental occlusion of a brain-supplying artery triggers tissue ischemia and subsequent inflammatory events that are initiated at the blood microvessel interface. Cytokine production and molecular adhesive events occur in the early moments following cerebral blood flow reduction, which underlie the transition from ischemic to inflammatory injury. Events both within the microvascular lumen and in the immediately surrounding tissue are involved. Cytokines, including TNF-alpha, IL-1 beta, IL-6, and PAF, are produced from the ischemic parenchyma and contribute to the endothelial cell expression of P-selectin, ICAM-1, and E-selectin. Platelet activation occurs paris passu and probably involves alpha-granule P-selectin to mediate PMN leukocyte-platelet interactions. Other integrin heterodimers are also involved in the early microvascular responses to ischemia. The response of the basal lamina and ECM is somewhat slower, entailing yet unproven mechanisms that most probably include the proteolytic processes of leukocyte transmigration. The modifications to microvascular structure are likely to affect both endothelial and astrocyte relationships, promote erythrocyte extravasation and hemorrhage, and contribute to tissue injury. Remodeling of the microvasculature, apparent in other tissues, involves a number of these processes. However, the enzymatic participants and regulating mechanisms are coming under study: the unraveling of regulatory mechanisms of adhesion receptor expression and their modulation, and the companion roles of integrins as mediators of structural integrity and intercellular signaling.
del Zoppo
G J
GJ
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA. grgdlzop@riscsm.scripps.edu
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004660:Encephalitis / Q000503:physiopathology*; D006801:Humans; D008833:Microcirculation; D011956:Receptors, Cell Surface / Q000378:metabolism
D015815:Cell Adhesion Molecules; D011956:Receptors, Cell Surface