期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 12, 期 3, 页码 409-414出版社
WILEY-BLACKWELL
DOI: 10.1111/jth.12487
关键词
bradykinin; coagulation; inflammation; ischemia; stroke; thrombosis
BackgroundSecondary microthrombosis is a major pathophysiologic mechanism leading to brain damage following transient mechanical vascular occlusion (TMVO), the most widely used experimental stroke model. Whether secondary microthrombosis also occurs in non-TMVO stroke models represents an important issue for clinical translation of antimicrothrombosis therapeutic strategies. ObjectivesTo assess the occurrence and the pathogenic role of secondary microthrombosis in two thrombin-induced stroke models in mice and non-human primates (Macaca mulatta). MethodsStroke was induced in mice and non-human primates by intra-arterial administration of recombinant thrombin. This method induces the formation of a fibrin-rich thrombus, which is spontaneously dissolved in the following hours by the endogenous fibrinolytic system. Perfusion-weighted imaging and fluorescent-lectin microangiography were performed after recanalization to detect secondary microthrombosis. Moreover, to investigate its pathogenic role, thrombin-induced stroke was induced in bradykinin receptorB1 (B1R) knockout mice, which are protected from the thromboinflammation responsible for secondary microthrombosis in TMVO models. ResultsReperfusion was stable and complete in all mice and non-human primates tested, revealing no secondary decrease in cerebral blood flow. No evidence of secondary microthrombosis was found in the two models. Accordingly, deficiency in B1R did not protect the mice from brain damage after thrombin-induced stroke. ConclusionsOur data demonstrate that secondary microthrombosis does not occur after thrombin-induced stroke. In view of this, the pathophysiologic roles of hematologic players promoting or protecting against secondary microthrombosis (such as factorXII, von Willebrand factor, and Tcells) deserve to be re-evaluated in non-TMVO stroke models.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据