ABSTRACT
While thrombotic obstruction of major brain-supplying arteries leads to symptomatic focal ischemic events, the microvasculature is the target of numerous insults that follow. Inflammatory cells, except for resident cells of the monocyte/macrophage lineage (microglia), pass through the microvasculature with circulatory flow, but stop and contribute to the development of cerebral infarction following blood flow cessation (Adams and Sidman, 1968; Graham, 1992; Moossy, 1985; Zülch and Kleihues, 1966). The participation of PMN and other leukocytes in the developing infarction requires their direct contact with the microvascular endothelium and the specialized perivascular cells of the brain. Following middle cerebral artery (MCA) occlusion and reperfusion PMN leukocytes contribute to microvascular obstruction, edema formation, and cellular necrosis and tissue infarction following the initial ischemic event (Hallenbeck et al., 1986; del Zoppo et al., 1991; Barone et al., 1995; Dereski et al., 1992; Garcia et al., 1994; Okada et al., 1994b; Mori et al., 1992). The interaction of PMN leukocytes with microvascular endothelium and the perivascular tissue requires the cooridnated expression of cellular adhesion receptors (Winn et al., 1993). Cytokine expression, up-regulation of endothelial adhesion receptors, and activation of leukocytes and platelets have been described in the early moments following MCA occlusion (reperfusion) in several experimental systems. Further, adherence of PMN leukocytes to vascular endothelium is required for local tissue injury resulting from superoxide free radical formation following the respiratory burst, and potent enzyme release (Babior et al., 1976; Mclntyre et al., 1995; Suematsu et al., 1993; Grisham et al., 1990). Leukocyte and platelet counter-receptors are exposed part passu. The thrust of this presentation is to summarize evidence for adhesion receptor participation in central nervous system injury, as exemplified by focal cerebral ischemia.
