Open Accessvon Willebrand factor contributes to poor outcome in a mouse model of intracerebral haemorrhage
Author(s) -
Ximin Zhu,
Yongliang Cao,
Lixiang Wei,
Ping Cai,
Haochen Xu,
Haiyu Luo,
Xiaofei Bai,
Lu Lu,
Jian-Ren Liu,
Wenying Fan,
Bing-Qiao Zhao
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep35901
Subject(s) - von willebrand factor , inflammation , medicine , blood–brain barrier , proinflammatory cytokine , pathophysiology , intercellular adhesion molecule 1 , microglia , myeloperoxidase , edema , immunology , pathology , central nervous system , platelet
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.