Metyrapone alleviates ischemic neuronal damage in the gerbil hippocampus

Naoto Adachi, Junfeng Chen, Keyue Liu, Takumi Nagaro, Tatsuru Arai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalEuropean Journal of Pharmacology
Volume373
Issue number2-3
DOIs
Publication statusPublished - Jun 4 1999

Keywords

  • (Gerbil)
  • Ca
  • Cerebral ischemia
  • Glucocorticoid
  • Glutamate
  • Hippocampus
  • Metyrapone

ASJC Scopus subject areas

  • Pharmacology

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