The number of insults and the cerebral damage after hypoxia/ischemia are altered after acute pretreatment with corticosterone and metyrapone

The role of glucocorticoids in neuronal viability is controversial. Most studies which describe the effects of glucocorticoids on ischemic brain damage use surgical adrenalectomy to induce a reduction in plasma corticosterone levels. In the present study we used metyrapone, a corticosterone synthesis inhibitor, to examine the effects of acute manipulation of corticosterone levels on neuronal damage and seizures. Shortly before transient hypoxia/ischemia, animals were subcutaneously injected with sesame oil, metyrapone, corticosterone or corticosterone+metyrapone. Both the neuronal damage and the percentage animals with seizures were found to correlate well with plasma corticosterone levels. This relation between affected area, seizures and corticosterone levels was confirmed when the rats were re-arranged into animals with and without seizures. However, corticosterone administration in metyrapone treated rats did not result (compared to MET treatment) in an increased neuronal damage. This suggests that the beneficial effects of metyrapone may be regulated by a corticosterone independent mechanism. © 1997 John Wiley & Sons, Ltd.