Focal cerebral ischemia in the cat: pretreatment with a kappa-1 opioid receptor agonist, CI-977.
The effects of the kappa-1 opioid receptor agonist (5R)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]-4- benzofuranacetamide monohydrochloride (CI-977) upon ischemic brain damage have been examined in 15 halothane-anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery (MCA), and the animals killed 6 h later. The amount of early ischemic brain damage was assessed in coronal sections at 16 predetermined stereotactic planes. Pretreatment with CI-977 (0.3 mg/kg i.v. followed by continuous infusion at 0.15 mg/kg/h until death), initiated 15 min prior to MCA occlusion, significantly reduced the volume of ischemic brain damage (from 2345 +/- 675 mm3 of the cerebral hemisphere in vehicle-treated cats to 1569 +/- 370 mm3 in CI-977-treated cats; P < 0.01). These data indicate that the kappa-1 opioid agonist CI-977 is neuroprotective in a model of focal cerebral ischemia in a gyrencephalic species where key systemic variables have been assessed throughout the entire post-ischemic period.
Wellcome Surgical Institute & Hugh Fraser Neuroscience Labs., University of Glasgow, UK.
K B
KB
Mackay
K
K
Kusumoto
D I
DI
Graham
J
J
McCulloch
D000818:Animals; D001572:Benzofurans / Q000097:blood / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002415:Cats; D002536:Cerebral Arteries / Q000502:physiology; D006400:Hematocrit; D006651:Histocytochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011759:Pyrrolidines / Q000097:blood / Q000627:therapeutic use*; D017473:Receptors, Opioid, kappa / Q000502:physiology*
D001572:Benzofurans; D001786:Blood Glucose; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C067110:enadoline