Deficiency of von Willebrand factor protects mice from ischemic stroke.
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.
Kleinschnitz
Christoph
C
Department of Neurology, University of Wuerzburg, Wuerzburg, Germany. christoph.kleinschnitz@mail.uni-wuerzburg.de
De Meyer
Simon F
SF
Schwarz
Tobias
T
Austinat
Madeleine
M
Vanhoorelbeke
Karen
K
Nieswandt
Bernhard
B
Deckmyn
Hans
H
Stoll
Guido
G
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
D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor