Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production

被引：154

作者：

Ravizza, Teresa ^{[1
]}

Noe, Francesco ^{[1
]}

Zardoni, Daniela ^{[1
]}

Vaghi, Valentina ^{[1
]}

Sifringer, Marco ^{[2
]}

Vezzani, Annamaria ^{[1
]}

机构：

[1] Mario Negri Inst Pharmacol Res, Lab Expt Neurol, Dept Neurosci, I-20156 Milan, Italy

[2] Charite, Dept Neonatol, D-13353 Berlin, Germany

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 31卷 / 03期

关键词：

D O I：

10.1016/j.nbd.2008.05.007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

An enhanced production of IL-1 beta in glia is a typical feature of epileptogenic tissue in experimental models and in human drug-refractory epilepsy. We show here that the selective inhibition of Interleukin Converting Enzyme (ICE), which cleaves the biologically active form of IL-1 beta using VX-765, blocks kindling development in rats by preventing IL-1 beta increase in forebrain astrocytes, without interfering with glia activation. The average afterdischarge duration was not altered significantly by VX-765. Up to 24 h after kindling completion and drug washout, kindled seizures could not be evoked in treated rats. VX-765 did not affect seizures or afterdischarge duration in fully kindled rats. These data indicate an antiepileptogenic effect mediated by ICE inhibition and that specific anti-IL-1 beta pharmacological strategies can be envisaged to interfere with epileptogenic mechanisms. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：327 / 333

页数：7

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