Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1β production
Abstract An enhanced production of IL-1β 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-1β using VX-...
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Veröffentlicht in: | Neurobiology of disease 2008-09, Vol.31 (3), p.327-333 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Abstract An enhanced production of IL-1β 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-1β using VX-765, blocks kindling development in rats by preventing IL-1β 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 suggest that specific anti-IL-1β pharmacological strategies can be envisaged to interfere with epileptogenic mechanisms. |
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ISSN: | 0969-9961 1095-953X |
DOI: | 10.1016/j.nbd.2008.05.007 |