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The effect of the kappa-opioid receptor agonist CI-977 in a rat model of focal cerebral ischaemia.

Abstract
The effect of a novel, highly potent and selective kappa-opioid receptor agonist CI-977 upon ischaemic brain damage and brain swelling has been examined in a rat model of focal cerebral ischaemia. Focal ischaemia was produced by the permanent occlusion of the left middle cerebral artery (MCA) during a brief period of halothane anaesthesia. The animals were sacrificed 24 h after MCA occlusion and the amount of ischaemic brain damage and swelling was assessed in coronal sections at 8 predetermined stereotactic planes. Treatment with CI-977 (0.03, 0.3 or 3 mg/kg), initiated 30 min prior to MCA occlusion (and at multiple times thereafter) produced dose-dependent reductions in the volumes of infarction and of brain swelling, with the most marked reductions being noted with CI-977 (0.3 mg/kg) in both infarction (reduced by 38% from controls; P less than 0.02) and swelling (reduced by 31%; P less than 0.002). There was an excellent correlation between the volume of brain swelling and ischaemic damage which was similar with saline-treated and CI-977-treated animals (overall correlation coefficient r = 0.896). These results indicate that CI-977 is effective in reducing infarction in a model of focal cerebral ischaemia, and that the reduction in brain swelling occurs in parallel with the reduction in ischaemic damage.
AuthorsK Kusumoto, K B Mackay, J McCulloch
JournalBrain research (Brain Res) Vol. 576 Issue 1 Pg. 147-51 (Mar 27 1992) ISSN: 0006-8993 [Print] Netherlands
PMID1325235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzofurans
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • enadoline
Topics
  • Animals
  • Benzofurans (pharmacology)
  • Brain Edema (prevention & control)
  • Cerebral Infarction (prevention & control)
  • Disease Models, Animal
  • Ischemic Attack, Transient (pathology, physiopathology)
  • Male
  • Pyrrolidines (pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid (drug effects, physiology)
  • Receptors, Opioid, kappa

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