ADDITIVE NEUROPROTECTIVE EFFECTS OF DEXTRORPHAN AND CYCLOHEXIMIDE IN RATS SUBJECTED TO TRANSIENT FOCAL CEREBRAL ISCHEMIA

Previous studies have implicated both excitotoxicity and apoptosis in the pathogenesis of cerebral infarction induced by focal ischemic insu lts. Here we tested the possibility that the NMDA antagonist, dextrorp han, and the protein synthesis inhibitor, cycloheximide, would produce additive protective effects in a rodent model of focal ischemia-reper fusion. Transient focal cerebral ischemia was induced by a 90 min peri od of ligation of the right middle cerebral artery and both common car otid arteries. Administration of either 30 mg/kg dextrorphan or 0.5 mg /kg cycloheximide, given i.p. 15 min before ischemia, reduced infarct volume by about 65%. When optimal concentrations of each drug were giv en together, infarct volume was reduced by 87% as measured 14 days lat er. These observations support the idea that both excitotoxicity, and apoptosis dependent on new protein synthesis, contribute to cerebral i nfarction after transient focal ischemia in the rat.