title: Additive neuroprotective effects of dextrorphan and cycloheximide in rats subjected to transient focal cerebral ischemia.
abstract: Previous studies have implicated both excitotoxicity and apoptosis in the pathogenesis of cerebral infarction induced by focal ischemic insults. Here we tested the possibility that the NMDA antagonist, dextrorphan, and the protein synthesis inhibitor, cycloheximide, would produce additive protective effects in a rodent model of focal ischemia-reperfusion. Transient focal cerebral ischemia was induced by a 90 min period of ligation of the right middle cerebral artery and both common carotid 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 given together, infarct volume was reduced by 87% as measured 14 days later. These observations support the idea that both excitotoxicity, and apoptosis dependent on new protein synthesis, contribute to cerebral infarction after transient focal ischemia in the rat.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: C
authors.initials: C
authors.lastname: Du
authors.forename: R
authors.initials: R
authors.lastname: Hu
authors.forename: C A
authors.initials: CA
authors.lastname: Csernansky
authors.forename: X Z
authors.initials: XZ
authors.lastname: Liu
authors.forename: C Y
authors.initials: CY
authors.lastname: Hsu
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology*; D003917:Dextrorphan / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D003917:Dextrorphan; D003513:Cycloheximide