PMID- 8856699 OWN - NLM STAT- MEDLINE DCOM- 19970306 LR - 20190718 IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 7 IP - 9 DP - 1996 Jun 17 TI - An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat. PG - 1465-8 AB - Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) cleaves pro-IL-1 beta to produce mature IL-beta, and is a member of a family of proteases implicated in apoptosis. Intracerebroventricular (i.c.v.) administration of an irreversible ICE inhibitor, z-VAD-DCB (1 pmol, 30 min before and 15 min, 2, 4, 6 and 8 h after surgery) markedly reduced (50 +/- 4%, p < 0.001) infarct volume measured 24 h after focal cerebral ischaemia (middle cerebral artery occlusion, MCAo) in the rat. Inhibition of damage was observed in the cortex (51 +/- 5% reduction) and striatum (42 +/- 6% reduction). These data implicate ICE in ischaemic neuronal death in vivo. Inhibition of ICE could reduce ischaemic damage either by preventing IL-1 beta synthesis or by inhibiting apoptosis or by both of these processes, and may provide a useful therapeutic approach to the inhibition of ischaemic brain damage. FAU - Loddick, S A AU - Loddick SA AD - School of Biological Sciences, University of Manchester, UK. FAU - MacKenzie, A AU - MacKenzie A FAU - Rothwell, N J AU - Rothwell NJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Cysteine Proteinase Inhibitors) RN - 0 (Interleukin-1) RN - 0 (Neuroprotective Agents) RN - 0 (Oligopeptides) RN - 0 (Recombinant Proteins) RN - 0 (z-VAD-DCB) RN - EC 3.4.22.- (Cysteine Endopeptidases) RN - EC 3.4.22.36 (Caspase 1) SB - IM EIN - Neuroreport 1999 Jun 23;10(9):inside back cov MH - Animals MH - Caspase 1 MH - Cell Line MH - Cells, Cultured MH - Cysteine Endopeptidases/*drug effects MH - Cysteine Proteinase Inhibitors/*therapeutic use MH - Enzyme Activation MH - Interleukin-1/*metabolism MH - Ischemic Attack, Transient/*prevention & control MH - Male MH - Molecular Weight MH - Monocytes/drug effects/metabolism MH - Neurons/*drug effects/pathology MH - Neuroprotective Agents/*therapeutic use MH - Oligopeptides/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Recombinant Proteins/antagonists & inhibitors EDAT- 1996/06/17 00:00 MHDA- 1996/06/17 00:01 CRDT- 1996/06/17 00:00 PHST- 1996/06/17 00:00 [pubmed] PHST- 1996/06/17 00:01 [medline] PHST- 1996/06/17 00:00 [entrez] AID - 10.1097/00001756-199606170-00004 [doi] PST - ppublish SO - Neuroreport. 1996 Jun 17;7(9):1465-8. doi: 10.1097/00001756-199606170-00004.