Combating innate inflammation: A new paradigm for acute treatment of stroke?

Abstract

Interferencewith early steps of platelet adhesion/activation by inhibition of the vonWillebrand factor (vWF) receptor glycoprotein (GP)Ib, its ligand vWF, or the collagen receptor GPVI, profoundly limits infarction in the mouse stroke model of transient middle cerebral artery occlusion (tMCAO). A similar pathogenic role was revealed for coagulation factor XII (FXII). Although these findings strongly suggest that microvascular thrombus formation is the leading pathophysiological event in acute stroke, recent studies have shown that thesemolecules have the additional capacity to guide inflammatory processes, thereby providing an intriguing alternative mechanistic explanation for these observations. Surprisingly,mice lacking T cells are also protected fromacute stroke, and these T cell effects are antigen independent. Thus, acute ischemic stroke can be redefined as a thrombo-inflammatory disorder, andmultifunctional molecules such as GPIb, GPVI, and FXII may provide new therapeutic targets linking inflammation and thrombus formation. © 2010 New York Academy of Sciences.