Metyrapone alleviates ischemic neuronal damage in the gerbil hippocampus

Transient forebrain ischemia was induced in gerbils, and the effect of a pr e-ischemic treatment with metyrapone (100 mg/kg) on delayed neuronal death in hippocampal CA1 neurons was evaluated. The effect of metyrapone on the i schemic release of amino acids in the CA1 region was also examined by micro dialysis. Hippocampal slices were used for the evaluation of the hypoxia-in duced intracellular Ca2+ increase by microfluorometry. The metyrapone treat ment morphologically improved the damage provoked by 3 min of ischemia, alt hough it did not alleviate the damage by 5 min. Ischemia for 3 min produced a 306% increase in the glutamate concentration in perfusates, and metyrapo ne suppressed the peak value to 42% of that in the control group. The exten t of the increase in fluorescence intensity by intracellular Ca2+ was lower by 16% in slices from metyrapone-treated animals than in controls 600 s af ter induction of hypoxia. The removal of Ca2+ from the perfusion medium sup pressed the hypoxic Ca2+ increase, and the increase was further reduced in slices pretreated with metyrapone. The increase in the level of endogenous glucocorticoids, which occurs in cerebral ischemia, may aggravate ischemic neuronal damage. (C) 1999 Elsevier Science B.V. All rights reserved.