Mitochondria, oxidative metabolism and cell death in XXXX .

@entity64 @entity39 @entity63 @entity26 @entity2388 @entity413 @entity855
@entity64 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 @entity855 and to changes in their properties that can contribute to the development of apoptotic and @entity39 cell death. In animal models of @entity64 , the limited availability of @entity413 and @entity26 directly impairs oxidative metabolism in severely @entity63 regions of the affected tissue and leads to rapid changes in @entity855 and other energy-related metabolites. In the less-severely @entity63 "penumbral" tissue, more moderate alterations develop in these metabolites, associated with near normal @entity413 use but impaired oxidative metabolism. This tissue remains potentially salvageable for at least the first few hours following @entity64 onset. Early restoration of blood flow can result in substantial recovery of energy-related metabolites throughout the affected tissue. However, @entity413 oxidation is markedly decreased due both to lower energy requirements in the post- @entity63 tissue and limitations on the mitochondrial oxidation of @entity2388 . 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 @entity63 and post- @entity63 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 @entity63 .
