The focus of this grant proposal is to elucidate the mechanisms for neurological morbidity associated with carbon monoxide (CO) poisoning.
The specific aims relate to evaluation of the biochemical events and functional deficits in brain which follow acute perivascular oxidative injury associated with CO poisoning in a rat model. There are three specific aims for this proposal: (1) Evaluate the changes in nitric oxide (NO) concentration and associated biochemical processes in brain after CO exposure, (2) Evaluate perivascular changes and immunological responses in brain following CO poisoning, (3) Evaluate the progression of brain injury and methods of protection. The ultimate goal is to determine the cascade of events initiated by CO that lead to neurological dysfunction. Exposure to CO raises the steady state concentration of NO. We hypothesize that perivascular changes triggered by NO-derived oxidants precipitate a series of pathological responses that begin during the CO exposure and continue for weeks. These changes lead to regional defects in parenchymal metabolism in brain and functional changes manifested as a learning deficit. The research plan is aimed to test the hypothesis that immune responses and the associated oxidative stress cause neurological injuries.
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| Mendelman, Avivit; Zarchin, Nili; Meilin, Sigal et al. (2002) Blood flow and ionic responses in the awake brain due to carbon monoxide. Neurol Res 24:765-72 |
| Atochin, D N; Fisher, D; Demchenko, I T et al. (2000) Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion. Undersea Hyperb Med 27:185-90 |
