Anesthesia-induced learning deficiency and brain hyperoxia

项目总结 麻醉在手术及其他临床过程中所致认知损害 近年来，程序一直是人们日益关注的焦点。不断增长的 文献已经证实，麻醉可能会导致病理影响，包括 细胞凋亡增加和髓鞘形成中断，最终导致学习 不足之处。然而，麻醉引起的这些变化背后的机制并不是 很好理解。我们之前已经报道过异氟醚的麻醉显著增加 脑组织中的氧气水平与清醒状态的比较。氧化应激是一个很好的- 已确定的神经毒性来源，已知可导致神经元和神经胶质细胞死亡 会破坏髓鞘的形成。因此，大脑高氧血症可能在解释 与麻醉相关的学习障碍。拟议的研究将研究 麻醉、脑氧水平与结构、生化和行为的关系 病理测量。在目标1中，我们将描述氧气、电生理反应、 和两种常见吸入麻醉剂(异氟烷和异氟醚)下的活性氧 七氟醚，)在空气和80%氧气中。在目标2中，我们将评估麻醉的效果 暴露在行为学习上。在目标3中，我们将评估结构和生化 麻醉暴露引起的脑部变化。这些研究将提供更深层次的 对麻醉生理学及其与血氧水平关系的理解 大脑。行为、核磁共振、氧气和电生理测量将提供信息 麻醉/高氧对脑结构和认知的短期和长期影响。

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.