Journal
NEUROBIOLOGY OF DISEASE
Volume 31, Issue 3, Pages 327-333Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2008.05.007
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Funding
- Fordazione Monzino
- EPICURE [LSH-CT-2006-037315]
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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.
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