An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat

Neuroreport. 1996 Jun 17;7(9):1465-8. doi: 10.1097/00001756-199606170-00004.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1
  • Cell Line
  • Cells, Cultured
  • Cysteine Endopeptidases / drug effects*
  • Cysteine Proteinase Inhibitors / therapeutic use*
  • Enzyme Activation
  • Interleukin-1 / metabolism*
  • Ischemic Attack, Transient / prevention & control*
  • Male
  • Molecular Weight
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Neurons / drug effects*
  • Neurons / pathology
  • Neuroprotective Agents / therapeutic use*
  • Oligopeptides / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / antagonists & inhibitors

Substances

  • Cysteine Proteinase Inhibitors
  • Interleukin-1
  • Neuroprotective Agents
  • Oligopeptides
  • Recombinant Proteins
  • z-VAD-DCB
  • Cysteine Endopeptidases
  • Caspase 1