Stroke, Vol 20, 1236-1240, Copyright © 1989 by American Heart Association
H Nishi, T Watanabe, H Sakurai, S Yuki and A Ishibashi
We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol
polyvinyl acetate into the left internal carotid artery, producing
permanent embolization in the left cerebral hemisphere, which developed
ipsilateral brain edema reproducibly. Edema was assessed 24 hours after
embolization by determining the brain water content and the sodium and
potassium concentrations. In this model, the free radical scavenger MCI-186
at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner.
At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and
improved the sodium-potassium balance to within the normal range in the
embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0
mg/kg i.v. did not significantly inhibit the development of brain edema.
Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest
that the cyclooxygenase metabolites of arachidonic acid liberated from
neuronal cell membrane phospholipids are not likely to be involved in the
pathogenesis of permanent brain edema induced by polyvinyl acetate. Our
results suggest that MCI-186 attenuates brain edema by suppressing the
production of lipoxygenase metabolites, including free radicals or lipid
peroxides, and that it may prove valuable for the treatment of brain edema
associated with cerebral ischemia.
ARTICLES
Effect of MCI-186 on brain edema in rats
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokolama, Japan.
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