Cyclosporin A-sensitive changes in mitochondrial glutathione are an early response to intrastriatal NMDA or forebrain ischemia in rats

Emad Zaidan, Michael Nilsson, Neil R. Sims

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    An intrastriatal injection of NMDA produced an increase in glutathione to 152% of control values in mitochondria isolated from striatum at 1 h later. Total tissue glutathione was not changed. The mitochondrial increase was largely reversed by 2 h. Glutathione content was not significantly affected in mitochondria from a part of the cerebral cortex that did not exhibit damage following intrastriatal NMDA. Glutathione was similarly increased in mitochondria from both cortex and striatum at 1 h after a short period of forebrain ischemia, confirming our previous findings. The increases in mitochondrial glutathione developed shortly after accumulations of mitochondrial calcium that have been observed previously. Intravenous injection of cyclosporin A immediately following either the NMDA treatment or reversal of the ischemic period partially inhibited the increases in glutathione in mitochondria from the affected brain subregions. These studies provide evidence that early changes sensitive to cyclosporin A develop in mitochondria under pathological conditions in the intact brain. These glutathione increases are consistent with an induction of the mitochondrial permeability transition in the affected tissue.

    Original languageEnglish
    Pages (from-to)2214-2217
    Number of pages4
    JournalJournal of Neurochemistry
    Volume73
    Issue number5
    DOIs
    Publication statusPublished - Nov 1999

    Keywords

    • Cyclosporin A
    • Excitotoxicity
    • Glutathione
    • Ischemia
    • Mitochondria
    • Mitochondrial permeability transition

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