21-aminosteroid reduces ion shifts and edema in the rat middle cerebral artery occlusion model of regional ischemia

U74006F is a member of a new family of steroid drugs called 21-aminosteroids, which are potent inhibitors of lipid peroxidation with little or no glucocorticoid or mineralocorticoid activity. We investigated the effects of U74006F on the early ionic edema produced by middle cerebral artery occlusion in rats. Intravenous doses of 3 mg/kg U74006F were given 10 minutes and 3 hours after occlusion. Tissue concentrations of Na⁺, K⁺, and water at and around the infarct site were measured by atomic absorption spectroscopy and by wet-dry weight measurements 24 hours after occlusion. Compared with vehicle treatment, U74006F treatment reduced brain water entry, Na⁺ accumulation, K⁺ loss, and net ion shift by 25-50% in most brain areas sampled in the frontal and parietal cortex. However, reductions of ionic edema were most prominent and reached significance (p<0.005, unpaired two-tailed t test) mostly in the frontoparietal and parietal cortex areas adjacent to the infarct site. Our findings suggest that a steroid drug without glucocorticoid or mineralocorticoid activity can reduce edema in cerebral ischemia but that the effects are largely limited to tissues in which collateral blood flow may be present.