Inflammatory responses to ischemia and reperfusion in the cerebral microcirculation

Abstract

Ischemia and reperfusion (I/R) has been shown to elicit an inflammatory response that is characterized by an increased production of reactive oxygen species, and the rolling, firm adhesion, and transendothelial migration of leukocytes in postcapillary venules. A rate-determining role for leukocyte-endothelial cell (L/E) adhesion in the initiation and propagation of reperfusion injury is supported by several reports that describe attenuated microvascular dysfunction and tissue injury following I/R in animals receiving neutralizing antibodies directed against certain leukocyte adhesion receptors and in mutant mice that are genetically deficient in these adhesion receptors The technique of intravital videomicroscopy has been applied to several tissues, including the brain, in order to directly observe the microcirculatory alterations and inflammatory responses that are elicited by I/R. The leukocyte- and platelet-endothelial cell adhesion responses to cerebral I/R are addressed and compared to responses observed in other postischemic vascular beds. The limited data available for the brain microcirculation support the potential of anti-leukocyte and anti-platelet strategies for stroke therapy.