Anesthesia-induced learning deficiency and brain hyperoxia

麻醉引起的学习缺陷和大脑高氧血症

• 批准号: 9330887
• 负责人: Daniil Aksenov
• 金额: $ 29.44万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330887
• 关键词: Adolescence; Adolescent; Age; Air; Anesthesia procedures; Anesthetics; Animal Model; Animals; Apoptosis; Attention; Behavioral; Biochemical; Biological Markers; Blinking; Brain; Breathing; Cell Death; Child; Choline; Clinical; Clinical Research; Cognition; Cognitive; Consumption; Development; Diffusion; Electrophysiology (science); Equilibrium; Exposure to; Gene Expression; General Anesthesia; Glutamates; Goals; Hippocampus (Brain); Hour; Hyperoxia; Impairment; Infant; Isoflurane; Lead; Learning; Learning Disabilities; Life; Light; Link; Literature; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Memory; Myelin; N-acetylaspartate; Neuroglia; Neurons; Operative Surgical Procedures; Oryctolagus cuniculus; Oxidative Stress; Oxygen; Pathologic; Pathology; Physiology; Play; Procedures; Production; Protocols documentation; Reactive Oxygen Species; Reporting; Risk; Signal Transduction; Source; Structure; Testing; anxiety-like behavior; awake; axon growth; behavior measurement; brain tissue; cerebral atrophy; clinical practice; conditioning; experimental study; field study; gamma-Aminobutyric Acid; infancy; myelination; neuron development; neuron loss; neuronal survival; neurotoxic; neurotoxicity; research study; response; sevoflurane

PROJECT SUMMARY Cognitive damage induced by anesthesia delivered in the course of surgery and other clinical procedures has been the focus of increasing attention in recent years. A growing body of literature has established that anesthesia can potentially lead to pathological effects including increased apoptosis and disruption of myelin formation, ultimately resulting in learning deficiencies. However, the mechanisms underlying these anesthesia-induced changes are not well understood. We have reported previously that isoflurane anesthesia significantly increases the oxygen level in brain tissue compared to the awake state. Oxidative stress is a well- established source of neurotoxicity which is known to induce neuronal and glial cell death and can disrupt myelin formation. Brain hyperoxia could therefore play a key role in explaining the learning impairments associated with anesthesia. The proposed study will examine the relationship between anesthesia, brain oxygen level, and structural, biochemical, and behavioral measures of pathology. In Aim 1, we will characterize oxygen, electrophysiological responses, and reactive oxygen species under two common inhaled anesthetics (isoflurane and sevoflurane,) in air and in 80% oxygen. In Aim 2, we will evaluate the effect of anesthesia exposure on behavioral learning. In Aim 3, we will evaluate the structural and biochemical changes in brain induced by anesthesia exposure. These studies will provide a deeper understanding of the physiology of anesthesia and its relationship with oxygen levels in the brain. Behavioral, MRI, oxygen, and electrophysiological measurements will provide information on the short- and long-term influence of anesthesia/hyperoxia on brain structure and cognition.

项目摘要 在手术和其他临床过程中进行的麻醉引起的认知损害 近年来，程序一直是增加关注的重点。越来越多的身体 文献已经确定，麻醉可能导致病理影响 增加凋亡和髓磷脂形成的破坏，最终导致学习 缺陷。但是，这些麻醉引起的变化的基础机制不是 理解。我们之前已经报道了异氟烷麻醉显着增加 与清醒状态相比，脑组织中的氧气水平。氧化应激是一种很好的 已知的神经毒性来源，已知会诱导神经元和神经胶质细胞死亡以及 会破坏髓鞘形成。因此，大脑高氧可以在解释 与麻醉相关的学习障碍。拟议的研究将检查 麻醉，脑氧水平与结构，生化和行为之间的关系 病理措施。在AIM 1中，我们将表征氧气，电生理反应， 在两种常见吸入麻醉药（异氟烷和 Sevoflurane，在空气中和80％的氧气中。在AIM 2中，我们将评估麻醉的效果 行为学习的曝光。在AIM 3中，我们将评估结构和生化 麻醉暴露引起的大脑变化。这些研究将提供更深的 了解麻醉的生理及其与氧气水平的关系 脑。行为，MRI，氧和电生理测量将提供信息 关于麻醉/高氧对大脑结构和认知的短期和长期影响。