Metyrapone Reduces Rat Brain Damage and Seizures after Hypoxia—Ischemia: An Effect Independent of Modulation of Plasma Corticosterone Levels?

Abstract

Hypoxia—ischemia is accompanied by abundant corticosterone secretion that could exacerbate brain damage after the insult. The authors demonstrate that the steroid synthesis inhibitor metyrapone (150 mg/kg subcutaneously) suppresses the hypoxia—ischemia-induced rise of plasma corticosterone levels (17.3 ± 3.6 μg/dL) when compared with corticosterone-treated animals (72.2 ± 4.8 μg/dL) immediately after hypoxia—ischemia. In parallel, metyrapone reduced brain damage ( P < 0.05). Moreover, none of the metyrapone-treated animals displayed seizures, whereas seven of eight corticosterone-treated animals had seizures after hypoxia—ischemia. Although corticosterone administration in metyrapone-treated animals elevated plasma corticosterone levels (39.0 ± 5.3 μg/dL), this did not result in a subsequent increase in brain damage and seizures when compared with metyrapone-treated animals. The authors conclude that metyrapone reduces brain damage and the incidence of seizures after hypoxia—ischemia but that this effect might partially be independent from its effect on modulating plasma corticosterone levels.