CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion
CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion
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DOI：
10.1161/01.cir.0000160349.42665.0c
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发表时间：
2005-04-05
期刊：
影响因子：
37.8
通讯作者：
Granger, DN
中科院分区：
文献类型：
--
作者：
Ishikawa, M;Vowinkel, T;Granger, DN
背景 - CD40/CD40 配体 (CD40L) 信号传导有助于脉管系统中的促炎和促血栓反应。短暂性脑缺血发作或中风后患者的 CD40/CD40L 表达升高。本研究的目的是探讨 CD40/CD40L 信号传导在大脑中动脉闭塞 (MCAO) 和再灌注引起的脑微血管功能障碍和组织损伤反应中的作用。 方法和结果 - 使用活体荧光显微镜观察野生型 (WT)、CD40 缺陷型和再灌注型的脑微循环。 CD40L 缺陷小鼠接受 1 小时 MCAO 和 4 小时再灌注。分别在再灌注4小时和1小时后测量毛细血管后微静脉中血小板和白细胞的粘附以及血管通透性。再灌注24小时后分析脑梗塞体积。 WT 小鼠中 MCAO 导致血小板和白细胞粘附升高，血/脑屏障功能受损。 CD40 缺陷和 CD40L 缺陷小鼠的血细胞募集和通透性增加均减弱。与 WT 小鼠相比，CD40 和 CD40L 缺陷小鼠的梗塞体积也减少。结论 - 我们的研究结果表明，CD40/CD40L 信号传导有助于炎症和血栓形成反应以及 MCAO 和再灌注诱导的脑梗塞。 CD40/CD40L二元体可能在缺血性中风的急性期发挥重要的致病作用。
Background - CD40/CD40 ligand (CD40L) signaling contributes to proinflammatory and prothrombogenic responses in the vasculature. CD40/CD40L expression is elevated in patients after a transient ischemic attack or stroke. The purpose of this study was to investigate the role of CD40/CD40L signaling in cerebral microvascular dysfunction and tissue injury response to middle cerebral artery occlusion (MCAO) and reperfusion.Methods and Results - Intravital fluorescence microscopy was used to visualize the cerebral microcirculation of wild-type (WT), CD40-deficient, and CD40L-deficient mice subjected to 1-hour MCAO and 4-hour reperfusion. The adhesion of platelets and of leukocytes and vascular permeability were measured in postcapillary venules after 4-hour and 1-hour reperfusions, respectively. Cerebral infarct volume was analyzed 24 hours after reperfusion. Platelet and leukocyte adhesion was elevated and blood/brain barrier function was compromised by MCAO in WT mice. Blood cell recruitment and increased permeability were blunted in both CD40-deficient and CD40L-deficient mice. Infarct volume was also reduced in CD40- and CD40L-deficient mice compared with WT mice.Conclusions - Our findings indicate that CD40/CD40L signaling contributes to inflammatory and prothrombogenic responses and brain infarction induced by MCAO and reperfusion. The CD40/CD40L dyad may play a significant pathogenic role in the acute phase of ischemic stroke.