title: Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats.
abstract: Both oxygen free radicals and excitatory amino acids have been implicated as important cellular toxins in ischemic brain. Recent in vitro studies suggest that there may be a mutual interaction between these two mediators. We explored the relation between oxygen free radicals and excitatory amino acids in the development of ischemic brain edema in vivo. Male Sprague-Dawley rats were treated with the free radical scavenger dimethylthiourea 1 hour before ischemia or with the excitotoxin antagonist MK-801 30 minutes before ischemia produced by occlusion of the middle cerebral artery. Groups of seven or eight animals were treated with vehicle, low-dose (375 mg/kg) dimethylthiourea, high-dose (750 mg/kg) dimethylthiourea, low-dose (0.5 mg/kg) MK-801, high-dose (2.0 mg/kg) MK-801, or both high-dose dimethylthiourea and low-dose MK-801. After 4 hours of ischemia, brain water content was determined. In eight vehicle-treated controls, mean +/- SEM water content of tissue in the center of the ischemic zone was 83.29 +/- 0.18%. A significant reduction of brain edema was observed in all drug-treated groups: for example, 50.2% (p less than 0.001) in the high-dose dimethylthiourea group, 53.7% (p less than 0.001) in the low-dose MK-801 group, and 66.4% (p less than 0.001) in the combined dimethylthiourea and MK-801 group. Combined treatment with dimethylthiourea and MK-801 provided no significant additive effect over that resulting from treatment with MK-801 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0718.
authors.forename: S M
authors.initials: SM
authors.lastname: Oh
authors.forename: A L
authors.initials: AL
authors.lastname: Betz
mesh_terms: D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D005609:Free Radicals; D008297:Male; D009498:Neurotoxins / Q000502:physiology*; D010100:Oxygen / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D005609:Free Radicals; D009498:Neurotoxins; D016291:Dizocilpine Maleate; C038983:1,3-dimethylthiourea; D012964:Sodium; D013890:Thiourea; D011188:Potassium; D010100:Oxygen