Deficiency of von Willebrand factor protects mice from ischemic stroke

We recently demonstrated that blockade of the platelet adhesion receptor glycoprotein (GP) Ibα protects mice from ischemic stroke. Although von Willebrand factor (VWF) is the major ligand for GPIbα, GPIbα can engage other counterreceptors on endothelial cells, platelets, and leukocytes (eg, Mac-1 or...

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Bibliographic Details
Published in:Blood 2009-04, Vol.113 (15), p.3600-3603
Main Authors: Kleinschnitz, Christoph, De Meyer, Simon F., Schwarz, Tobias, Austinat, Madeleine, Vanhoorelbeke, Karen, Nieswandt, Bernhard, Deckmyn, Hans, Stoll, Guido
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Ischemia - pathology
Brain Ischemia - physiopathology
Brain Ischemia - prevention & control
Hematologic and hematopoietic diseases
Infarction, Middle Cerebral Artery - pathology
Infarction, Middle Cerebral Artery - physiopathology
Infarction, Middle Cerebral Artery - prevention & control
Magnetic Resonance Imaging
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Neurology
Platelet Adhesiveness - physiology
Platelet Glycoprotein GPIb-IX Complex - metabolism
Vascular diseases and vascular malformations of the nervous system
von Willebrand Factor - genetics
von Willebrand Factor - metabolism
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Summary:We recently demonstrated that blockade of the platelet adhesion receptor glycoprotein (GP) Ibα protects mice from ischemic stroke. Although von Willebrand factor (VWF) is the major ligand for GPIbα, GPIbα 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 GPIbα-VWF pathway might become a promising therapeutic option.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-09-180695