The complement cascade as a therapeutic target in intracerebral hemorrhage.
The complement cascade as a therapeutic target in intracerebral hemorrhage.
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DOI：
10.1016/j.expneurol.2009.07.018
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发表时间：
2009-10
影响因子：
5.3
通讯作者：
Connolly, E. Sander, Jr.
中科院分区：
文献类型：
--
作者：
Ducruet, Andrew F.;Zacharia, Brad E.;Hickman, Zachary L.;Grobelny, Bartosz T.;Yeh, Mason L.;Sosunov, Sergey A.;Connolly, E. Sander, Jr.
脑出血(ICH)是第二种最常见和最致命的中风形式。目前，还没有针对这种毁灭性疾病的药物治疗策略。继出血后的最初机械损伤后，继发性脑损伤通过直接细胞损伤和炎症级联反应进行，触发粒细胞和单核细胞的渗透，小胶质细胞的激活，血脑屏障的破坏，从而导致脑水肿。补体的级联反应在脑出血后继发性损伤的发病机制中起核心作用，但补体近端活化的具体机制尚不完全清楚。补体成分(C3)裂解后的脑损伤通过平行但相互关联的过敏性毒素介导的炎症和继发于膜攻击的复合体驱动的红细胞溶解的直接毒性途径进行。补体激活在脑出血后的恢复过程中也可能起着重要的生理作用。因此，详细了解补体激活的功能效应随时间的变化对于开发这一靶点作为治疗脑出血的令人兴奋的翻译策略至关重要。
Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood–brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage.
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DOI：
10.1084/jem.133.4.885
发表时间：
1971-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hill JH;Ward PA
通讯作者：
Ward PA
影响因子：
4.2
作者：
Bellander, BM;Singhrao, SK;Svensson, M
通讯作者：
Svensson, M
影响因子：
4.1
作者：
Hua, Y;Xi, GH;Hoff, JT
通讯作者：
Hoff, JT
清除： 凋亡过程中经常被遗忘的阶段
影响因子：
2.5
作者：
Fadok, VA
通讯作者：
Fadok, VA
影响因子：
6.3
作者：
Ducruet, Andrew F.;Hassid, Benjamin G.;Connolly, E. Sander
通讯作者：
Connolly, E. Sander