Roles of inflammation and the activated protein C pathway in the brain edema associated with cerebral venous sinus thrombosis.
Roles of inflammation and the activated protein C pathway in the brain edema associated with cerebral venous sinus thrombosis.
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DOI：
10.1161/strokeaha.109.562983
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发表时间：
2010-01
期刊：
影响因子：
8.3
通讯作者：
Granger DN
中科院分区：
文献类型：
--
作者：
Nagai M;Terao S;Yilmaz G;Yilmaz CE;Esmon CT;Watanabe E;Granger DN
血脑屏障（BBB）通透性增加、脑水肿和出血是脑静脉窦血栓形成（CVST）的重要后果。本研究的目的是确定蛋白C途径在实验性CVST引起的BBB通透性和水肿中的作用。还评价了中性粒细胞募集的作用。在CVST小鼠模型中监测水肿、血脑屏障通透性、白细胞-内皮细胞粘附（LECA）和炎性细胞因子水平。在接受APC中和抗体的野生型小鼠（WT）和内皮蛋白C受体过表达小鼠（EPCR-tg）中评估活化蛋白C（APC）的作用。使用抗CD 18抗体（Ab）和抗中性粒细胞血清（ANS）评价中性粒细胞受累。CVST后48小时观察到脑水肿和BBB通透性和LECA增加。APC免疫阻断加剧了这些反应，而EPCR-tg表现出钝化的反应，如用ANS或CD 18 Ab处理的WT。蛋白C通路保护大脑免受CVST的有害微血管反应，这种反应似乎与炎症细胞的募集有关。
Increased blood brain barrier (BBB) permeability, brain edema and hemorrhage are important consequences of cerebral venous sinus thrombosis (CVST). The objective of this study was to define the role of the protein C pathway, in the BBB permeability and edema elicited by experimental CVST. The role of neutrophil recruitment was also evaluated. Edema, BBB permeability, leukocyte-endothelial cell adhesion (LECA) and inflammatory cytokine levels were monitored in a murine model of CVST. The role of activated protein C (APC) was assessed in wild type mice (WT) receiving APC neutralizing antibody and in endothelial protein C receptor overexpressing mice (EPCR-tg). Neutrophil involvement was evaluated using an anti-CD18 antibody (Ab) and anti-neutrophil serum (ANS). Brain edema and increases in BBB permeability and LECA were noted 48 hrs after CVST. APC immunoblockade exacerbated these responses, while EPCR-tg exhibited blunted responses, as did WT treated with either ANS or the CD18 Ab. The protein C pathway protects the brain against the deleterious microvascular responses to CVST, a response that appears to be linked to the recruitment of inflammatory cells.