Brain mitochondrial responses to postischemic reperfusion: A role for calcium and hydrogen peroxide?

Neil R. Sims, Michelle F. Anderson, Leanne M. Hobbs, Jason A. Powell, Emad Zaidan

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    9 Citations (Scopus)


    During early recirculation following global brain ischemia, mitochondria are exposed to markedly elevated Ca2+ concentrations and a short-lived production of reactive oxygen species, including hydrogen peroxide (H2O2). A brief increase in mitochondrial Ca2+ and a subsequent increase in mitochondrial glutathione content have been observed. In the present study, we have confirmed the increase in mitochondrial glutathione in a rat model of global forebrain ischemia. This change was not inhibited by treatment of the rats with FK506, contrasting with our previous finding that cyclosporin A partially blocked the increase. These results suggest that induction of the mitochondrial permeability transition may be necessary for the increase in glutathione content in these organelles. To further investigate possible mitochondrial responses during early postischemic reperfusion, mitochondria isolated from normal brain were exposed to Ca2+ and H2O2, under conditions similar to those in intact cells. Respiratory activity was substantially modified when the mitochondria were exposed to Ca2+ and H2O2 together. Two distinct and largely noninteracting mechanisms apparently accounted for the responses to these agents. The effects of Ca2+, but not H2O2, were inhibited by cyclosporin A, again implicating the permeability transition in some of the mitochondrial changes. Copyright (C) 2000 S. Karger AG, Basel.

    Original languageEnglish
    Pages (from-to)366-375
    Number of pages10
    JournalDevelopmental Neuroscience
    Issue number5-6
    Publication statusPublished - Sept 2000

    Bibliographical note

    Copyright 2007 Elsevier B.V., All rights reserved.


    • Calcium
    • FK506
    • Glutathione
    • Hydrogen peroxide
    • Ischemia
    • Mitochondria
    • Oxidative phosphorylation
    • Permeability transition


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