Transient forebrain
ischemia was induced in gerbils, and the effect of a pre-ischemic treatment with
metyrapone (100 mg/kg) on delayed neuronal death in hippocampal CA1 neurons was evaluated. The effect of
metyrapone on the ischemic release of
amino acids in the CA1 region was also examined by microdialysis. Hippocampal slices were used for the evaluation of the
hypoxia-induced intracellular Ca2+ increase by microfluorometry. The
metyrapone treatment morphologically improved the damage provoked by 3 min of
ischemia, although it did not alleviate the damage by 5 min.
Ischemia for 3 min produced a 306% increase in the
glutamate concentration in perfusates, and
metyrapone suppressed the peak value to 42% of that in the control group. The extent of the increase in fluorescence intensity by intracellular Ca2+ was lower by 16% in slices from
metyrapone-treated animals than in controls 600 s after induction of
hypoxia. The removal of Ca2+ from the perfusion medium suppressed 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.