CO POISONING IN THE CONTEXT OF A REPERFUSION INJURY

这项拨款提案的重点是阐明与一氧化碳(CO)中毒相关的神经系统疾病的机制。具体目的是评价CO中毒大鼠急性血管周围氧化损伤后的生化事件和脑功能缺陷。本研究的目的有三个：(1)评价一氧化碳暴露后脑内一氧化氮(NO)浓度及相关生化过程的变化；(2)评价一氧化碳中毒后脑血管周围的变化及免疫反应；(3)评价脑损伤的进展及防护措施。最终目标是确定一氧化碳引发的导致神经功能障碍的一连串事件。暴露于CO可使NO的稳态浓度升高。我们假设，由NO衍生的氧化剂引发的血管周围改变导致了一系列的病理反应，这些反应始于一氧化碳暴露期间，并持续数周。这些变化导致大脑实质代谢的区域性缺陷和表现为学习障碍的功能变化。这项研究计划旨在测试免疫反应和相关的氧化应激导致神经损伤的假设。

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.