U50488 reduces the severity of tissue damage in a rabbit model of focal cerebral ischemia

Marsha A. Widmayer, Tina D. Turner, Jeffrey L. Browning, David S. Baskin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Many pharmacotherapies for stroke that have been successful in the laboratory have proven to be ineffective in the clinical setting, often because patients do not arrive for treatment until hours after the onset of the ischemic insult. Kappa opioid treatment of cerebral ischemia has been successful in the cat and mouse with treatment delays of up to 6 h. The purpose of the present study was to develop a model of delayed kappa opioid treatment of cerebral ischemia in the rabbit. Fourteen rabbits underwent permanent, unilateral occlusion of the internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital, microsurgical approach. At 6 h postocclusion, animals received a blinded bolus injection and continuous infusion of either saline or the kappa agonist, U50488. Survival was not improved after U50488 treatment. U50488 treatment did, however, reduce areas of severe tissue damage and increase areas of modest tissue damage. This suggests U50488 arrested the progression of damage from noninfarcted to fully infarcted tissue. The present results show beneficial effects of delayed treatment with kappa agonists in a species similar in vasculature to humans, and much less costly than primates or cats.

Original languageEnglish (US)
Pages (from-to)211-223
Number of pages13
JournalMolecular and Chemical Neuropathology
Issue number3
StatePublished - Aug 1 1994


  • Cerebral ischemia
  • infarction
  • kappa agonist
  • kappa receptors
  • neuronal damage
  • neuroprotection
  • rabbit

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Molecular Biology


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