title: Deficiency of von Willebrand factor protects mice from ischemic stroke.
abstract: We recently demonstrated that blockade of the platelet adhesion receptor glycoprotein (GP) Ibalpha protects mice from ischemic stroke. Although von Willebrand factor (VWF) is the major ligand for GPIbalpha, GPIbalpha can engage other counterreceptors on endothelial cells, platelets, and leukocytes (eg, Mac-1 or P-selectin) potentially involved in stroke outcome. To further analyze whether VWF is of particular relevance for stroke development, VWF(-/-) mice underwent 60 minutes of middle cerebral artery occlusion. After 24 hours, VWF(-/-) mice had significantly smaller infarctions (P< .05) and less severe neurologic deficits (P< .01) compared with controls. This effect was sustained after 1 week, and intracranial bleeding was absent in VWF(-/-) mice as revealed by serial magnetic resonance imaging. Hydrodynamic injection of a VWF-encoding plasmid restored the susceptibility for stroke in VWF(-/-) mice. This study indicates that VWF is critically involved in cerebral ischemia. Hence, targeted inhibition of the GPIbalpha-VWF pathway might become a promising therapeutic option.
authors.affiliation: Department of Neurology, University of Wuerzburg, Wuerzburg, Germany. christoph.kleinschnitz@mail.uni-wuerzburg.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.forename: Simon F
authors.initials: SF
authors.lastname: De Meyer
authors.forename: Tobias
authors.initials: T
authors.lastname: Schwarz
authors.forename: Madeleine
authors.initials: M
authors.lastname: Austinat
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Hans
authors.initials: H
authors.lastname: Deckmyn
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010973:Platelet Adhesiveness / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor