Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production
Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production
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DOI：
10.1016/j.nbd.2008.05.007
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发表时间：
2008-09-01
影响因子：
6.1
通讯作者：
Vezzani, Annamaria
中科院分区：
文献类型：
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作者：
Ravizza, Teresa;Noe, Francesco;Vezzani, Annamaria
在实验模型和人类药物难治性癫痫中，神经胶质中IL-1 β的产生增强是致癫痫组织的典型特征。我们在这里表明，选择性抑制白细胞介素转化酶（ICE），使用VX-765切割IL-1 β的生物活性形式，通过阻止前脑星形胶质细胞中IL-1 β的增加来阻断大鼠点燃的发展，而不干扰神经胶质细胞的活化。VX-765未显著改变平均后放电持续时间。点燃完成和药物洗脱后24 h，治疗组大鼠不能诱发点燃癫痫发作。VX-765不影响癫痫发作或后放电持续时间在完全点燃大鼠。这些数据表明ICE抑制介导的抗癫痫作用，并且可以设想特异性抗IL-1 β药理学策略来干扰癫痫机制。(C)2008年爱思唯尔公司All rights reserved.
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.