General Anesthesia During Early Childhood and Brain Development

项目总结/摘要 大量数据表明，全身麻醉（GA）会导致神经毒性和长期的缺陷， 年轻动物的学习和记忆。每年有数百万的年轻人患有GA。具有重大 考虑到早期GA可能导致大脑和认知功能异常， 可能会产生终身影响的发展。尽管动物实验的结果令人担忧， 研究可能适用于人类，关于可能对大脑产生不良影响的证据有限， 人类早期GA的认知发展。使用神经成像技术的研究尤其有限。 我们在这个建议中的目标是了解GA在幼儿期对随后的影响。 大脑结构，脑功能和认知，通过比较青少年与GA在儿童早期， 其他方面与没有GA的对照受试者相似。我们将评估GA对磁共振成像的影响 脑组织体积和组成、白色物质完整性、局部脑活动的成像测量 在长期和工作记忆任务，和休息状态的功能连接，以及认知测试 成绩和学术成就。基于我们的初步数据，我们的假设是，早期GA将 与较低的白色物质体积和减少的白色物质完整性、记忆相关变化相关 在长期和工作记忆任务中的大脑活动，受损的视觉长期记忆识别， 和更高频率的低成就测试分数。拟议的研究还旨在 比较在出生至3岁范围内不同年龄发生的GA，以及伴随的高与低 侵入性手术我们将主要关注没有明显中枢神经系统问题的儿童 或可能构成混杂因素的潜在风险因素。我们还假设， 无论上述假设在何种程度上得到证实，对于第一次遗传算法，所观察到的影响都将较小 老年人的暴露，例如，3年时暴露的影响小于近出生时;且具有可比性 对于高与低侵入性手术，当其他因素如GA持续时间和性别得到控制时。我们 还假设任何这样的影响将随着GA持续时间的增加而增加。我们还将探索 共患病的影响（即，早产）和区域麻醉对GA的后果。这些发现 可以解决在动物研究中发现的GA对大脑影响的潜在机制，如细胞凋亡， 少突胶质细胞和神经元和/或在关键发育期发生的其他神经毒性。的 拟议的研究将有助于填补知识的关键差距，有关遗传算法的后果，在早期 儿童对大脑和认知发展的影响，并提供有关其风险的信息， 实践的临床护理的儿童谁有GA。

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.