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 (e.g. 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 min of middle cerebral artery occlusion. After 24 h, VWF(-/-) mice had significantly smaller infarctions (p<0.05) and less severe neurological deficits (p<0.01) compared to 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.