Prevention of Ischemic Brain Mitochondrial Injury by Lidoflazine
Viability of the brain is dependent on maintenance of ionic and electrochemical gradients within neurons as well as within subcellular components. Of particular interest is neuronal handling of calcium. Under aerobic, steady-state conditions intracellular Ca2+ concentration is maintained at basal levels of approximately 0.1µM by ATP-dependent ionic pumps, as compared to extracellular levels of 1.0 mM. In the brain, more than 80% of ATP is generated through mitochondrial oxidative phosphorylation (Fiskum, 1983, 1985). If oxidative phosphorylation were interrupted, ATP synthesis would be greatly impaired, thus preventing maintenance of ionic gradients, with potentially catastrophic consequences. Loss of calcium homeostasis has been linked to the initiation of various degradative processes including activation of phospholipases (Fiskumet al., 1985), lipid peroxidation (McCord, 1985), vascular spasm (Borgerset al., 1983), induction of coagulative necrosis (Farber, 1982), and eventually cell death (Borgerset al., 1983).
KeywordsCerebral Ischemia Calcium Antagonist Brain Mitochondrion Mitochondrial Electron Transport Chain Mitochondrial Oxidative Phosphorylation
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