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: 10686998
• 负责人: Daniil Aksenov
• 金额: $ 34.62万
• 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/10686998
• 关键词: Adolescence; Adult; Affect; Age; Anesthesia procedures; Animals; Axon; Behavioral; Brain; Cell Count; Child; Childhood; Clinical; Cognitive; Control Groups; Data; Development; 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; Human; Hyperoxia; Impairment; Individual; Induction of Apoptosis; Interneurons; Laser-Doppler Flowmetry; Learning; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Methods; Microinjections; Neonatal; Neurons; Oryctolagus cuniculus; Oxygen; Physiological; Predictive Value; Preventive treatment; Publishing; Pyramidal Cells; Regulation; Rest; Signal Transduction; Somatosensory Cortex; Testing; Time; Visualization; Work; awake; behavior test; behavioral deficiency; brain tissue; diagnostic biomarker; diagnostic tool; early detection biomarkers; hippocampal pyramidal neuron; infancy; neuron development; neurotoxicity; neurovascular; optogenetics; patch clamp; pharmacologic; 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 每年有数百万儿童接受全身麻醉，动物和人体研究表明， 表明，在早期暴露于麻醉会影响神经元的发育， 儿童和青少年时期表现出来的行为和学习障碍。 然而，人们对可用于评估这些损伤的方法知之甚少。 我们的初步和发表的数据表明，区域静息状态功能的变化， MRI（rsfMRI）能反映局部神经元网络的状态，并具有预测价值 因为麻醉导致的学习障碍区域rsfMRI依赖于局部的调节， 脑组织氧气根据已发表的和初步的数据，我们假设脑组织 氧和局部rsfMRI调节由GABA能神经元（中间神经元）调节， 新生儿麻醉破坏了这种调节的发展， rsfMRI信号的特征在目标1中，我们将确定负责 正常及新生儿脑损伤后局部rsfMRI与脑组织氧调节的关系 通过使用脑组织氧，BOLD功能磁共振成像，电生理记录， 局部药理学和光遗传学方法。在目标2中，我们将确定 区域rsfMRI和脑组织氧波动的发展受到新生儿的影响 麻醉暴露，并找到rsfMRI可以预测未来行为的时间点 缺陷行为测试，局部rsfMRI，脑组织氧和神经元活动将被 在新生儿麻醉暴露后的多个时间点记录， 组拟议工作的结果将提供一个清晰的画面，如何监管的 脑组织氧受新生儿麻醉暴露的影响， 静息态功能磁共振成像预测学习障碍的转化价值