Mitochondria, oxidative metabolism and cell death in stroke

Neil Sims, Hakan Muyderman

    Research output: Contribution to journalReview articlepeer-review

    502 Citations (Scopus)


    Stroke most commonly results from occlusion of a major artery in the brain and typically leads to the death of all cells within the affected tissue. Mitochondria are centrally involved in the development of this tissue injury due to modifications of their major role in supplying ATP and to changes in their properties that can contribute to the development of apoptotic and necrotic cell death. In animal models of stroke, the limited availability of glucose and oxygen directly impairs oxidative metabolism in severely ischemic regions of the affected tissue and leads to rapid changes in ATP and other energy-related metabolites. In the less-severely ischemic "penumbral" tissue, more moderate alterations develop in these metabolites, associated with near normal glucose use but impaired oxidative metabolism. This tissue remains potentially salvageable for at least the first few hours following stroke onset. Early restoration of blood flow can result in substantial recovery of energy-related metabolites throughout the affected tissue. However, glucose oxidation is markedly decreased due both to lower energy requirements in the post-ischemic tissue and limitations on the mitochondrial oxidation of pyruvate. A secondary deterioration of mitochondrial function subsequently develops that may contribute to progression to cell loss. Mitochondrial release of multiple apoptogenic proteins has been identified in ischemic and post-ischemic brain, mostly in neurons. Pharmacological interventions and genetic modifications in rodent models strongly implicate caspase-dependent and caspase-independent apoptosis and the mitochondrial permeability transition as important contributors to tissue damage, particularly when induced by short periods of temporary focal ischemia.

    Original languageEnglish
    Pages (from-to)80-91
    Number of pages12
    JournalBiochimica et Biophysica Acta-Molecular Basis of Disease
    Issue number1
    Publication statusPublished - Jan 2010


    • Apoptosis
    • Energy metabolism
    • Focal ischemia
    • Mitochondria
    • Necrosis
    • Stroke


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