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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES005211-14
Application #
6619406
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Kirshner, Annette G
Project Start
1989-07-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2005-07-31
Support Year
14
Fiscal Year
2003
Total Cost
$396,250
Indirect Cost
Name
University of Pennsylvania
Department
Emergency Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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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