Inhibition of arachidonic acid-induced vasogenic brain edema by the non-glucocorticoid 21-aminosteroid U74006F.
The effects of the novel non-glucocorticoid 21-aminosteroid U74006F on arachidonic acid (AA)-induced vasogenic brain edema were examined in rats. Vasogenic edema was assessed in terms of the extent of Evan's blue extravasation after subcortical micro-injection of AA indicative of blood-brain barrier disruption. U74006F, given i.v. at 15 min before the AA, produced a dose-related reduction in the area of subsequent Evan's blue staining measured in a coronal brain cross-section through the injection site. The highest dose tested (1.0 mg/kg) resulted in a 65% decrease in the area of blood-brain barrier disruption in comparison to that seen in vehicle-treated animals (P less than 0.0001). The mechanism of the anti-edema effect of U74006F is discussed in relation to the previously demonstrated ability of the compound to inhibit oxygen free radical-mediated lipid peroxidation.
Hall
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Central Nervous System Diseases Research Unit, Upjohn Company, Kalamazoo, MI 49001.
Travis
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D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D001929:Brain Edema / Q000139:chemically induced / Q000188:drug therapy*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats
D001095:Arachidonic Acids; D008054:Lipid Peroxides; D011281:Pregnatrienes; D016718:Arachidonic Acid; C053355:tirilazad