Neurological disorders are common and occur with higher frequency following head trauma. Some neurological disorders may be caused by oxidative damage to the nervous tissue. Evidence is now accumulating, as detailed later, to indicate that iron, most likely as small molecular weight complexes, is playing a key role in oxidative damage to nervous tissue. The strongest evidence to support this concept has been developed in experimentally induced epilepsy. In addition, strong supporting data has been shown in an experimental model of spinal cord injury. Also, recent work shows that iron, as low molecular weight complexes, accumulates in ischemic brain and appears to play a role in the oxidative damage that occurs apparently in reoxygenation of this tissue. All of the work clearly indicates that iron is toxic to brain and the mechanism of its toxicity is apparently due to peroxidation of this tissue. Our research work in brain has strongly implicated that oxidative damage to brain is iron mediated, and it appears that the site of initiation of peroxidation may be in the electron transport chain of mitochondria. We have also found that dopamine synthesis in striatum synaptosomes is very sensitive to peroxidation and this damage causes significant changes in membrane structural parameters. In an attempt to understand the basic mechanisms of iron induced oxidative damage to nervous tissue, we propose to determine if the initiation site of peroxidation is in the electron transport chain of brain mitochondria; examine the basic mechanisms why Alpha-tocopherol and selenium protect against iron induced damage; and, also, examine the effect of peroxidative damage in cerebral cortex synaptosomes as to modification of these goals will yield basic information necessary to the understanding of oxidative damage in nervous tissue at the molecular level, which, when integrated with knowledge at the physiological and anatomical level, will hopefully explain the processes that occur in the initiation of the development of some neurological disorders.
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