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

Abstract

Interference with early steps of platelet adhesion/activation by inhibition of the von Willebrand 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 these molecules 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 from acute stroke, and these T cell effects are antigen independent. Thus, acute ischemic stroke can be redefined as a thrombo-inflammatory disorder, and multifunctional molecules such as GPIb, GPVI, and FXII may provide new therapeutic targets linking inflammation and thrombus formation.

• Authors: Guido Stoll, Christoph Kleinschnitz, Bernhard Nieswandt
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1207 Pg. 149-54 (Oct 2010) ISSN: 1749-6632 [Electronic] United States
• PMID: 20955438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2010 New York Academy of Sciences.

Chemical References

• Platelet Membrane Glycoproteins
• platelet membrane glycoprotein VI
• von Willebrand Factor
• von Willebrand factor receptor
• Factor XII

Topics

• Animals
• Disease Models, Animal
• Factor XII (antagonists & inhibitors)
• Humans
• Immunity, Innate
• Inflammation (blood, immunology, therapy)
• Mice
• Platelet Activation
• Platelet Membrane Glycoproteins (antagonists & inhibitors)
• Stroke (blood, immunology, therapy)
• T-Lymphocytes (immunology)
• von Willebrand Factor (antagonists & inhibitors)