Complement activation in the brain after experimental intracerebral hemorrhage
Complement activation in the brain after experimental intracerebral hemorrhage
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DOI：
10.3171/jns.2000.92.6.1016
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发表时间：
2000-06-01
影响因子：
4.1
通讯作者：
Hoff, JT
中科院分区：
文献类型：
--
作者：
Hua, Y;Xi, GH;Hoff, JT
Object.脑出血后脑水肿的形成似乎与红细胞溶解和血红蛋白释放有关。红细胞溶解可能由补体级联介导，然后触发实质损伤。在这项研究中，作者研究了ICH后补体级联反应是否被激活，以及抑制补体是否减轻血肿周围的脑水肿。本研究分为三个部分。在第一部分中，将100 μ l自体血注入大鼠右侧基底节，并在脑内注入后24和72小时处死动物。通过免疫组织化学分析，对他们的大脑进行了补体因子C9，C3 d和clusterin（一种天然存在的补体抑制剂）的测试。在研究的第二部分中，在注射100 μ l血液后24或72小时处死大鼠。使用Western印迹分析定量C9和clusterin蛋白。在第三部分中，大鼠接受100 μ l血液或100 μ l血液加10 μ g N-乙酰肝素（一种补体激活抑制剂）。24或72小时后处死动物，测定脑组织含水量和脑组织离子含量。Western印迹分析表明，在输注100 μ l自体血后24小时，血肿周围的C9增加了6倍。在72小时时检测到显著的血肿周围C9免疫反应性。脑出血后，Ephterin也增加，72小时后在神经元中表达。加入N-乙酰肝素显著减少24小时同侧基底节脑水肿的形成（78.5 +/- 0.5%，对照组动物为81.6 +/- 0.8%，p < 0.001）和72小时时（80.9 +/- 2.2%，对照组动物为83.6 +/- 0.9%，p < 0.05）。发现ICH引起脑中的补体激活。脑出血后补体激活和膜攻击复合物的形成参与脑水肿的形成。阻断补体级联反应可能是治疗脑出血的重要步骤。
Object. Brain edema formation following intracerebral hemorrhage (ICH) appears to be partly related to erythrocyte lysis and hemoglobin release. Erythrocyte lysis may be mediated by the complement cascade, which then triggers parenchymal injury. In this study the authors examine whether the complement cascade is activated after ICH and whether inhibition of complement attenuates brain edema around the hematoma.Methods. This study was divided into three parts. In the first part, 100 mu l of autologous blood was infused into the rats' right basal ganglia, and the animals were killed at 24 and 72 hours after intracerebral infusion. Their brains were tested for complement factors C9, C3d, and clusterin (a naturally occurring complement inhibitor) by using immunohistochemical analysis. In the second part of the study, the rats were killed at 24 or 72 hours after injection of 100 mu l of blood. The C9 and clusterin proteins were quantitated using Western blot analysis. In the third part, the rats received either 100 mu l of blood or 100 mu l of blood plus 10 mu g of N-acetylheparin (a complement activation inhibitor). Then they were killed 24 or 72 hours later for measurement of brain water and ion contents. It was demonstrated on Western blot analysis that there had been a sixfold increase in C9 around the hematoma 24 hours after the infusion of 100 mu l of autologous blood. Marked perihematomal C9 immunoreactivity was detected at 72 hours. Clusterin also increased after ICH and was expressed in neurons 72 hours later. The addition of N-acetylheparin significantly reduced brain edema formation in the ipsilateral basal ganglia at 24 hours (78.5 +/- 0.5% compared with 81.6 +/- 0.8% in control animals, p < 0.001) and at 72 hours (80.9 +/- 2.2% compared with 83.6 +/- 0.9% in control animals, p < 0.05) after ICH.Conclusions. It was found that ICH causes complement activation in the brain. Activation of complement and the formation of membrane attack complex contributes to brain edema formation after ICH. Blocking the complement cascade could be an important step in the therapy for ICH.