Related resources
Search for item elsewhere
University researcher(s)
Academic department(s)
An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat.
Loddick S, MacKenzie A, Rothwell NJ
Neuroreport. 1996;7( 9):1465-8.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere. Alternatively, request a copy from the Library's Document supply service.
Abstract
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.
Keyword(s)
Animals; Caspase 1; Cell Line; Cells, Cultured; Enzyme Activation; Male; Molecular Weight; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't; antagonists & inhibitors: Recombinant Proteins; drug effects: Cysteine Endopeptidases; drug effects: Monocytes; drug effects: Neurons; prevention & control: Ischemic Attack, Transient; secretion: Interleukin-1; therapeutic use: Cysteine Proteinase Inhibitors; therapeutic use: Neuroprotective Agents; therapeutic use: Oligopeptides