Stroke, Vol 22, 915-921, Copyright © 1991 by American Heart Association
SM Oh and AL Betz
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)
ARTICLES
Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats
Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0718.
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