Neutrophil accumulation and neutrophil-mediated tissue damage in the postischemic brain have been well documented in numerous animal studies and in humans during the past three decades. Activation of vascular endothelial cells and leukocytes by local and humoral factors increases the cell surface expression of a family of adhesion molecules termed selectins, which promote low-affinity leukocyte rolling over the surface of endothelial cells. This process is an obligatory preliminary step leading to subsequent firm attachment, at which point leukocytes can exert numerous cytotoxic effects leading to microvascular plugging, stasis and thrombosis. Advances in our understanding of the role of inflammation and neutrophil-endothelial cell interactions in the pathophysiology of tissue ischemia and reperfusion have provided the current impetus for pharmacologic approaches that treat acute ischemic stroke by interrupting selectin-ligand interaction.
ASJC Scopus subject areas
- Drug Discovery