Focal cerebral ischemia in the cat: pretreatment with a kappa-1 opioid receptor agonist, CI-977

Abstract

The effects of the kappa-1 opioid receptor agonist (5R)-(5α,7α,8β)- N-methyl- N-[7-(1-pyrrolidinyl)-1-oxaspirol[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 ± 675mm 3 of the cerebral hemisphere in vehicle-treated cats to 1569 ± 370mm 3 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.