Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-D-aspartate glutamate receptors improves hemorrhagic stroke outcome

被引：18

作者：

Gaberel, Thomas ^{[1
,2
]}

Macrez, Richard ^{[1
]}

Gauberti, Maxime ^{[1
]}

Montagne, Axel ^{[1
]}

Hebert, Marie ^{[1
]}

Petersen, Karl-Uwe ^{[3
]}

Touze, Emmanuel ^{[4
]}

Agin, Veronique ^{[1
]}

Emery, Evelyne ^{[1
,2
]}

Ali, Carine ^{[1
]}

Vivien, Denis ^{[1
]}

机构：

[1] Univ Caen Lower Normandy, Serine Proteases & Pathophysiol Neurovasc Unit, GIP Cyceron, Inserm,UMR S U919, F-14074 Caen, France

[2] Caen Univ Hosp, Dept Neurosurg, Caen, France

[3] PAION Deutschland GmbH, Aachen, Germany

[4] Hop St Anne, Dept Neurol, F-75674 Paris, France

来源：

NEUROPHARMACOLOGY | 2013年 / 67卷

关键词：

Cerebral hemorrhage; Neurotoxicity; Immunotherapy; Tissue plasminogen activator; EXPERIMENTAL INTRACEREBRAL HEMORRHAGE; BLOOD-BRAIN-BARRIER; CELL-DEATH; MODEL; EDEMA; RAT; THROMBOLYSIS; INFLAMMATION; COLLAGENASE; INHIBITION;

D O I：

10.1016/j.neuropharm.2012.11.023

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Ischemic and hemorrhagic strokes have different etiologies, but share some pathogenic mechanisms, including a pro-neurotoxic effect of endogenous tissue plasminogen activator (tPA) via N-methyl-D-Aspartate (NMDA) receptors. Thus, in a model of intracerebral hemorrhage in rats, we investigated the therapeutic value of a strategy of immunotherapy (alpha ATD-GluN1 antibody) preventing the interaction of tPA with NMDA receptors. We found that a single intravenous injection of aATD-GluN1 reduced brain edema, neuronal death, microglial activation and functional deficits following intracerebral hemorrhage, without affecting the hematoma volume. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：267 / 271

页数：5

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