D-JNKi, a peptide inhibitor of c-Jun N-terminal kinase, promotes functional recovery after transient focal cerebral ischemia in rats

被引：45

作者：

Esneault, E. ^{[1
,2
]}

Castagne, V. ^{[1
]}

Moser, P. ^{[1
]}

Bonny, C. ^{[3
]}

Bernalidin, M. ^{[2
]}

机构：

[1] Porsolt & Partners Pharmacol, ZA Suhards, F-53940 Le Genest St Isle, France

[2] Univ Caen, CNRS, CERVOxy Grp Hypoxia & Cerebrovasc Pathophysiol, CYCERON,UMR 6185, F-14074 Caen, France

[3] CHU Vaudois, Univ Hosp, Div Med Genet, CH-1011 Lausanne, Switzerland

来源：

NEUROSCIENCE | 2008年 / 152卷 / 02期

关键词：

JNK; behavior; neurological score; adhesive removal test; object recognition; beam walking test;

D O I：

10.1016/j.neuroscience.2007.12.036

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The c-Jun-N-terminal kinase (JNK) pathway has been shown to play an important role in excitotoxic neuronal death and several studies have demonstrated a neuroprotective effect of D-JNKi, a peptide inhibitor of JNK, in various models of cerebral ischemia. We have now investigated the effect of D-JNKi in a model of transient focal cerebral ischemia (90 min) induced by middle cerebral artery occlusion (MCAo) in adult male rats. D-JNKi (0.1 mg/kg), significantly decreased the volume of infarct, 3 days after cerebral ischemia. Sensorimotor and cognitive deficits were then evaluated over a period of 6 or 10 days after ischemia and infarct volumes were measured after behavioral testing. In behavioral studies, D-JNKi improved the general state of the animals as demonstrated by the attenuation of body weight loss and improvement in neurological score, as compared with animals receiving the vehicle. Moreover, D-JNKi decreased sensorimotor deficits in the adhesive removal test and improved cognitive function in the object recognition test. In contrast, D-JNKi did not significantly affect the infarct volume at day 6 and at day 10. This study shows that D-JNKi can improve functional recovery after transient focal cerebral ischemia in the rat and therefore supports the use of this molecule as a potential therapy for stroke. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：308 / 320

页数：13

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