General Anesthesia During Early Childhood and Brain Development

幼儿期和大脑发育期间的全身麻醉

• 批准号: 10641652
• 负责人: ROBERT I BLOCK
• 金额: $ 58.1万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641652
• 关键词: Academic achievement; Address; Adolescent; Adverse effects; Age; Anesthetics; Animals; Anisotropy; Apoptosis; Behavioral; Birth; Brain; Brain Injuries; Brain region; Central Nervous System; Characteristics; Child; Child Care; Childhood; Cognition; Cognitive; Conduction Anesthesia; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Environment; Ethnic Origin; Exclusion; Exposure to; Family; Frequencies; Functional Magnetic Resonance Imaging; Future; Gender; General Anesthesia; Human; Impaired cognition; Individual; Knowledge; Label; Laboratories; Language; Learning; Magnetic Resonance Imaging; Measures; Mediation; Memory; Neurologic; Neurons; Oligodendroglia; Pattern; Performance; Premature Birth; Procedures; Public Health; Race; Research; Rest; Risk; Risk Factors; Short-Term Memory; Statistical Data Interpretation; Structure; Structure-Activity Relationship; Techniques; Testing; United States National Institutes of Health; Visual; Visual impairment; Volatilization; achievement test; brain tissue; clinical practice; cognitive development; cognitive function; cognitive testing; comorbidity; critical developmental period; early childhood; gray matter; human old age (65+); juvenile animal; long term memory; memory recognition; myelination; neuroimaging; neurotoxicity; performance tests; premature; primary outcome; recruit; regional difference; white matter

PROJECT SUMMARY/ABSTRACT Substantial data indicate that general anesthesia (GA) causes neurotoxicity and long-term deficits in learning and memory in young animals. Millions of young human children have GA annually. This is of great public health concern given the possibility that early GA could cause abnormalities in brain and cognitive development that might have lifelong consequences. Although there is great concern that findings from animal studies may apply to humans, limited evidence exists concerning the possible adverse effects on brain and cognitive development of early GA in humans. Studies using neuroimaging techniques are especially limited. Our objective in this proposal is to understand the consequences of GA during early childhood on subsequent brain structure, brain function, and cognition by comparing adolescents with GA during early childhood to otherwise similar control subjects without GA. We will evaluate the effects of GA on magnetic resonance imaging measures of brain tissue volume and composition, white matter integrity, regional brain activity during long-term and working memory tasks, and resting state functional connectivity, as well as cognitive test performance and academic achievement. Our hypotheses, based on our preliminary data, are that early GA will be associated with lower white matter volumes and diminished white matter integrity, memory-related changes in brain activity during long-term and working memory tasks, impaired visual long-term memory recognition, and a higher frequency of very low achievement test scores. The proposed research additionally aims to compare GA occurring at varying ages within the range of birth to 3 years, and accompanying high vs. low invasive procedures. We will focus primarily on children without significant central nervous system problems or potential risk factors that might constitute confounding factors. We additionally hypothesize that to whatever extent the hypotheses stated above are confirmed, the observed effects will be smaller for first GA exposure at older ages, e.g., smaller effects from exposure at 3 years relative to near birth; and be comparable for high vs. low invasive procedures, when other factors such as GA duration and gender are controlled. We also hypothesize that any such effects will increase with increasing GA duration. We will additionally explore influences of comorbidity (i.e., premature birth) and regional anesthesia on consequences of GA. The findings could address potential mechanisms of the brain effects of GA found in animal studies, such as apoptosis of oligodendrocytes and neurons and/or other neurotoxicity that occur during critical developmental periods. The proposed research will help fill a critical gap in knowledge concerning the consequences of GA during early childhood on brain and cognitive development, and provide information about its risks that might change best practices for clinical care of children who have GA.

项目摘要/摘要 大量数据表明，全身麻醉（GA）会导致神经毒性和长期缺陷 年轻动物的学习和记忆。数百万年的年轻儿童每年有GA。这很棒 鉴于早期GA可能导致大脑和认知异常的可能性，公共卫生的关注 可能会带来终生后果的发展。尽管有动物的发现非常关心 研究可能适用于人类，存在有限的证据，表明对大脑可能不利影响 早期GA在人类中的认知发展。使用神经影像技术的研究特别有限。 我们在此提案中的目标是了解幼儿期间GA的后果 大脑结构，大脑功能和认知在幼儿期间与GA的青少年进行比较 否则，没有GA的类似控制对象。我们将评估GA对磁共振的影响 脑组织体积和组成，白质完整性，区域大脑活动的成像测量 在长期和工作记忆任务以及静止状态功能连接以及认知测试中 表现和学术成就。根据我们的初步数据，我们的假设是早期的GA将会 与较低的白质体积和白质完整性减少，与内存相关的变化有关 在长期和工作记忆任务中的大脑活动中，视觉长期记忆识别受损， 以及更高的成就测试分数的较高频率。拟议的研究还旨在 比较出生年龄在3年内的年龄变化的GA，并伴随高与低 侵入性程序。我们将主要关注没有重大中枢神经系统问题的儿童 或可能构成混杂因素的潜在危险因素。我们还假设 无论上述假设的确认程度如何 在年龄较大的年龄较大的情况下，相对于近出生的3岁暴露会导致较小的影响；并可比 对于高侵入性程序，当控制其他因素（例如GA持续时间和性别）时。我们 还假设任何此类效应都会随着GA持续时间的增加而增加。我们还将探索 合并症的影响（即早产）和区域麻醉对GA的后果的影响。发现 可以解决动物研究中GA的大脑影响的潜在机制，例如 关键发育期间发生的少突胶质细胞和/或其他神经毒性。这 拟议的研究将有助于填补有关早期GA后果的知识的关键差距 大脑和认知发展的童年，并提供有关其风险可能改变最佳风险的信息 具有GA的儿童的临床护理实践。