title: von Willebrand factor contributes to poor outcome in a mouse model of intracerebral haemorrhage.
abstract: Spontaneous intracerebral haemorrhage (ICH) is the most devastating stroke subtype and has no proven treatment. von Willebrand factor (VWF) has recently been demonstrated to promote inflammation processes. The present study investigated the pathophysiological role of VWF after experimental ICH. Functional outcomes, brain edema, blood-brain barrier (BBB) permeability, cerebral inflammation and levels of intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) were measured in a mouse model of ICH induced by autologous blood injection. We show that VWF were increased in the plasma and was accumulated in the perihematomal regions of mice subjected to ICH. Injection of VWF resulted in incerased expression of proinflammatory mediators and activation of ICAM-1 and MMP-9, associated with elevated myeloperoxidase, recruitment of neutrophils and microglia. Moreover, mice treated with VWF showed dramatically decreased pericyte coverage, more severe BBB damage and edema formation, and neuronal injury was increased compared with controls. In contrast, blocking antibodies against VWF reduced BBB damage and edema formation and improved neurological function. Together, these data identify a critical role for VWF in cerebral inflammation and BBB damage after ICH. The therapeutic interventions targeting VWF may be a novel strategy to reduce ICH-related injury.
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Ximin
authors: X
authors: Zhu
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Yongliang
authors: Y
authors: Cao
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Lixiang
authors: L
authors: Wei
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Ping
authors: P
authors: Cai
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Haochen
authors: H
authors: Xu
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Haiyu
authors: H
authors: Luo
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Xiaofei
authors: X
authors: Bai
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Lu
authors: L
authors: Lu
authors: Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors: Jian-Ren
authors: JR
authors: Liu
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Wenying
authors: W
authors: Fan
authors: State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors: Bing-Qiao
authors: BQ
authors: Zhao
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000097:blood / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000097:blood / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011379:Prognosis; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; C090509:Icam1 protein, mouse; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse