Carbon monoxide exposure and anesthesia-induced neurotoxicity

一氧化碳暴露和麻醉引起的神经毒性

• 批准号: 9000221
• 负责人: Richard J Levy
• 金额: $ 27.89万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9000221
• 关键词: Carbon; monoxide; exposure; anesthesia; induced

Commonly used anesthetics cause widespread neurodegeneration in the developing mammalian brain. Neurotoxicity occurs due to caspase activation via the mitochondrial pathway of apoptosis followed by activation of death receptor and neurotrophic-factor activated pathways. Carbon monoxide (CO) has anti- apoptotic properties and exhaled endogenous CO is commonly re-breathed during low-flow anesthesia (LFA) in infants and children resulting in sub-clinical CO exposure. There is a major gap in our knowledge because it is unknown if CO exposure inhibits anesthesia-induced neuroapoptosis. The specific hypothesis behind this proposal is that low concentrations of inspired CO prevent anesthesia-induced neurotoxicity. The experiments outlined in this proposal are aimed to determine the mechanism of CO-mediated inhibition of isoflurane-induced neuroapoptosis, to identify the neurologic consequences of simultaneous CO and isoflurane exposure in newborn mice, and to develop a large animal model of CO re-breathing during LFA. This proposal will lay the groundwork for development of CO re-breathing during LFA as a preventative intervention designed to protect against anesthesia-induced neurodegeneration.

常用的麻醉剂会导致哺乳动物大脑发育中广泛的神经变性。 神经毒性是由于 caspase 通过线粒体凋亡途径激活而发生的 死亡受体和神经营养因子激活途径的激活。一氧化碳 (CO) 具有抗 细胞凋亡特性和呼出的内源性 CO 通常在低流量麻醉 (LFA) 期间重新呼吸 婴儿和儿童会导致亚临床 CO 暴露。我们的知识存在重大差距，因为 目前尚不清楚 CO 暴露是否会抑制麻醉诱导的神经细胞凋亡。背后的具体假设 该提议认为，低浓度的吸入二氧化碳可以预防麻醉引起的神经毒性。这 本提案中概述的实验旨在确定 CO 介导的抑制机制 异氟烷诱导的神经细胞凋亡，以确定同时 CO 和 新生小鼠的异氟烷暴露，并开发 LFA 期间再呼吸 CO 的大型动物模型。 该提案将为 LFA 期间开发二氧化碳再呼吸作为预防措施奠定基础 旨在防止麻醉引起的神经变性的干预措施。