Blocking TRAIL-DR5 signaling with soluble DR5 reduces delayed neuronal damage after transient global cerebral ischemia

被引：46

作者：

Cui, Min ^{[1
]}

Wang, Limei ^{[2
]}

Hang, Xiaohong ^{[3
]}

Ma, Xuelian ^{[1
]}

Liu, Yugang ^{[4
]}

Yang, Mingfeng ^{[5
]}

Liu, Kejing ^{[1
]}

Wei, Xinbing ^{[6
]}

Zhou, Zhiqiang ^{[4
]}

Chen, Youhai H. ^{[7
]}

Sun, Wensheng ^{[3
]}

机构：

[1] Shandong Univ, Sch Med, Dept Physiol, Jinan 250012, Shandong, Peoples R China

[2] Ocean Univ China, Sch Med & Pharmaceut, Qingdao 266003, Shandong, Peoples R China

[3] Shandong Univ, Sch Med, Dept Immunol, Jinan 250012, Shandong, Peoples R China

[4] Shandong Univ, Sch Med, Dept Pathol & Pathophysiol, Jinan 250012, Shandong, Peoples R China

[5] Taishan Med Coll, Affiliated Hosp, Dept Neurol, Tai An 271000, Shandong, Peoples R China

[6] Shandong Univ, Sch Med, Dept Pharmacol, Jinan 250012, Shandong, Peoples R China

[7] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

NEUROBIOLOGY OF DISEASE | 2010年 / 39卷 / 02期

基金：

中国国家自然科学基金;

关键词：

TRAIL; DR5; Apoptosis; Brain ischemia; APOPTOSIS-INDUCING LIGAND; CELL-DEATH; T-CELLS; FOREBRAIN ISCHEMIA; DECOY RECEPTORS; BRAIN; MICE; ACTIVATION; MECHANISMS; ASTROCYTES;

D O I：

10.1016/j.nbd.2010.03.018

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Mechanisms underlying delayed selective neuronal death after global cerebral ischemia remain to be clarified. Here, we report a critical role for tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of cerebral ischemia. C57BL/6j mice were subjected to transient global brain ischemia. RT-PCR and immunohistochemistry showed that the expression of TRAIL and DR5 was upregulated following transient ischemia-reperfusion. Dual immunofluorescence analysis indicated that TRAIL expression was significantly more pronounced in astrocytes and activated microglia/macrophages, whereas DR5 expression was more pronounced in neurons, which had a good correlation with the distribution of apoptotic cells. Treatment with soluble DR5 reduced ischemic cell death after transient global ischemia through blocking the interaction of endogenous TRAIL with DR5. These results indicate that TRAIL plays a deleterious role in the pathogenesis of delayed neuronal damage after global cerebral ischemia and inhibition of TRAIL function in the brain may represent a novel neuroprotective strategy to treat ischemic stroke. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：138 / 147

页数：10

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