The novel 21-aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat.

摘要: The present study evaluated the effect of nonglucocorticoid 21-aminosteroid U74006F, an inhibitor iron-dependent lipid peroxidation, on development regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP injury moderate severity centered over left parietal cortex (2.5-2.6 atms). Fifteen minutes injury, animals randomly received i.v. bolus either U74006F (3 mg/kg, n 21) followed by a second mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, 15). An additional group 12 surgically prepared but uninjured served as preinjury controls. At 48 sacrificed tissue assayed for water content cation concentrations. With use specific gravimetric techniques, no significant differences observed in posttraumatic between drug- control-treated animals. However, using wet weight/dry weight methodology, we found that administration significantly reduced right hippocampus (contralateral site injury) compared saline-treated (p less than 0.05). also prevented postinjury increase concentrations ipsilateral 0.05) thalamus 0.03). Regional potassium unaltered drug treatment. Administration mortality, from 28% control zero treated 0.01). These results suggest peroxidation may be involved pathophysiological sequelae 21-aminosteroids beneficial treatment