Developmental disruption of brain tissue oxygen regulation and deficiency of learning after neonatal anesthesia exposure

新生儿麻醉暴露后脑组织氧调节的发育障碍和学习缺陷

• 批准号: 10378327
• 负责人: Daniil Aksenov
• 金额: $ 29.17万
• 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 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10378327
• 关键词: Adolescence; Adult; Affect; Age; Anesthesia procedures; Animals; Apoptosis; Axon; Behavioral; Brain; Cell Count; Child; Childhood; Clinical; Cognitive; Control Groups; Data; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Electrophysiology (science); Excitatory Amino Acid Antagonists; Exposure to; Frequencies; Functional Magnetic Resonance Imaging; Future; GABA Antagonists; General Anesthesia; Goals; Halorhodopsins; Health; Hippocampus (Brain); Human; Hyperoxia; Impairment; Individual; Interneurons; Laser-Doppler Flowmetry; Learning; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Methods; Microinjections; Neonatal; Neurons; Oryctolagus cuniculus; Oxygen; Pharmacology; Physiological; Predictive Value; Preventive treatment; Publishing; Pyramidal Cells; Regulation; Rest; Signal Transduction; Somatosensory Cortex; Testing; Time; Work; awake; base; behavior test; behavioral deficiency; brain tissue; diagnostic biomarker; early detection biomarkers; hippocampal pyramidal neuron; infancy; neuron development; neurotoxicity; neurovascular; optogenetics; patch clamp; receptor; tool

PROJECT SUMMARY Millions of children undergo general anesthesia each year, and animal and human studies have indicated that exposure to anesthesia at an early age can impact neuronal development, leading to behavioral and learning impairments that manifest later in childhood and adolescence. However, little is known about the methods which can be used to evaluate these impairments. Our preliminary and published data suggest that changes in regional resting state functional MRI (rsfMRI) can reflect the status of local neuronal networks and can have a predictive value for anesthesia-induced learning deficiency. Regional rsfMRI depends on the regulation of local brain tissue oxygen. Based on published and preliminary data we hypothesize that brain tissue oxygen and regional rsfMRI regulation are modulated by GABAergic neurons (interneurons) but neonatal anesthesia disrupts the development of this modulation and produces a specific signature on the rsfMRI signal. In Aim 1 we will determine the mechanisms responsible for regional rsfMRI and brain tissue oxygen regulation under normal conditions and after neonatal anesthesia exposure by using brain tissue oxygen, BOLD fMRI, electrophysiological recordings, local pharmacological and optogenetic approach in adults. In Aim 2 we will determine how the development of regional rsfMRI and brain tissue oxygen fluctuations is affected by neonatal anesthesia exposure and find time points when rsfMRI can predict the future behavioral deficiency. Behavioral tests, local rsfMRI, brain tissue oxygen, and neuronal activity will be recorded in across multiple time points after neonatal anesthesia exposure and in the control group. The results of the proposed work will provide a clear picture of how the regulation of brain tissue oxygen is affected by neonatal anesthesia exposure and will offer strong translational value of resting-state fMRI to predict learning deficiency.

项目摘要 每年数以百万计的儿童进行全身麻醉，动物和人类研究有 表明在幼年时暴露于麻醉会影响神经元发展，导致 在童年和青春期后期体现的行为和学习障碍。 但是，对于可用于评估这些障碍的方法知之甚少。 我们的初步和发布的数据表明，区域静止状态功能的变化 MRI（RSFMRI）可以反映局部神经元网络的状态，并且可以具有预测值 麻醉引起的学习缺乏。区域RSFMRI取决于局部的调节 脑组织氧气。根据已发布和初步数据，我们假设脑组织 氧气和区域RSFMRI调节受GABA能神经元（中间神经元）调节，但 新生儿麻醉破坏了该调节的发展，并产生特定的 RSFMRI信号上的签名。在AIM 1中，我们将确定负责的机制 区域RSFMRI和脑组织氧气在正常条件下和新生儿之后 通过使用脑组织氧，大胆的fMRI，电生理记录的麻醉暴露， 成人局部药理和光遗传学方法。在AIM 2中，我们将确定如何 区域RSFMRI和脑组织氧气波动的发展受新生儿的影响 当RSFMRI可以预测未来的行为时，麻醉暴露并找到时间点 不足。行为测试，局部RSFMRI，脑组织氧和神经元活性将是 新生儿麻醉后的多个时间点记录在多个时间点中 团体。拟议工作的结果将清楚地了解如何调节 脑组织氧受到新生儿麻醉的影响，将提供强大的 静止状态fMRI的翻译价值以预测学习缺陷。