The effect of the kappa-opioid receptor agonist CI-977 in a rat model of focal cerebral ischaemia.
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.
Kusumoto
K
K
Wellcome Surgical Institute and Hugh Fraser Neuroscience Labs., University of Glasgow, UK.
Mackay
K B
KB
McCulloch
J
J
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001929:Brain Edema / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000517:prevention & control*; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa
D001572:Benzofurans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C067110:enadoline