Neurobehavioral and Neuroimaging Effects of Traffic Exposure in Children

描述（由申请人提供）：拟议的研究将解决以下假设：在大脑发育的关键时期暴露于交通相关空气污染（TRAP）与神经行为改变显著相关，包括认知、注意力、记忆、执行功能、整体智力、神经运动功能、行为调节和大脑解剖学和生理学改变的缺陷。产前和幼儿期暴露于环境神经毒物与神经行为缺陷和大脑结构改变有关。最近的毒理学证据表明，TRAP是金属、元素和有机碳、多环芳烃以及细颗粒和超细颗粒物质的复杂混合物，能够诱导神经炎症和穿过血脑屏障的易位，导致直接暴露于大脑。本研究的目的是确定是否 在脑发育的早期阶段暴露于增加水平的TRAP的儿童在儿童期具有神经行为缺陷，并评估TRAP暴露对脑结构、组织和功能的生理影响。辛辛那提儿童过敏和空气污染研究（CCAAPS）是一项前瞻性队列研究，为实现这些目标提供了一个非凡的机会。招募CCAAPS队列研究交通废气与过敏性疾病和哮喘发生之间的关系。参加CCAAPS的儿童必须在出生时居住在距离主要公路不到400米或超过1500米的地方。使用环境空气监测和空间模型对儿童早期接触TRAP的情况进行了描述。在1-4岁和7岁时收集了临床健康评估、生物标志物、健康问卷以及所有家庭、日托和学校地点的地址。这项研究具有创新性，因为它利用了所有收集的健康，空气监测和建模数据，并扩展了CCAAPS队列的重点，以研究儿童早期TRAP暴露对神经行为和神经影像学结果的影响。在11-12岁时将进行一系列精心挑选的有效和可靠的测试，以评估神经行为发育。另一个独特的方面是提出的嵌套研究儿童与高和低暴露于TRAP在幼儿期，以评估生理影响的TRAP对发育中的大脑使用定量磁共振成像（MRI）。预期的结果将解决普遍存在的环境暴露的潜在神经毒性的科学知识的重大差距，对未来的研究和公共健康产生深远的影响。 公共卫生相关性：儿童早期暴露于交通相关空气污染（TRAP）与神经行为和神经影像学结果之间的关系尚未得到彻底研究。拟议研究的目的是确定在大脑发育的关键时期暴露于TRAP水平升高的儿童是否通过一系列有效和可靠的测试改变了儿童时期的神经行为，并使用定量磁共振成像（MRI）评估TRAP暴露对大脑结构，组织和功能的生理影响。这些结果将填补与TRAP暴露与神经行为和中枢神经系统影响之间关系相关的当前科学知识的重要空白。

DESCRIPTION (provided by applicant): The proposed study will address the hypothesis that exposure to traffic-related air pollution (TRAP) during critical periods of brain development is significantly associated with altered neurobehavior including deficits in cognition, attention, memory, executive function, global intelligence, neuromotor function, behavioral regulation, and altered brain anatomy and physiology. Exposure to environmental neurotoxicants prenatally and during early childhood has been associated with neurobehavioral deficits and altered brain structure. Recent toxicological evidence suggests that TRAP, a complex mixture of metals, elemental and organic carbon, polycyclic aromatic hydrocarbons, and fine and ultrafine particulate matter, is capable of inducing neuroinflammation and translocation across the blood-brain barrier resulting in direct exposure to the brain. The aims of this study are to determine if children exposed to increased levels of TRAP during early stages of brain development have neurobehavioral deficits in childhood and to assess the physiologic impact of TRAP exposure on brain structure, organization, and function. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective cohort study, provides an extraordinary opportunity to accomplish these aims. The CCAAPS cohort was recruited to examine the association between traffic exhaust and the development of allergic disease and asthma. Children enrolled in CCAAPS must have resided either less than 400 m or greater than 1500 m from a major highway at the time of their birth. TRAP exposure during early childhood has been characterized using ambient air monitoring and spatial models. Clinical health assessments, biomarkers, health questionnaires, and addresses of all home, daycare, and school locations have been collected at ages 1-4 and 7. The proposed study is innovative as it exploits all of the collected health, air monitoring, and modeling data and extends the focus of the CCAAPS cohort to examine the impact of early childhood TRAP exposure on neurobehavior and neuroimaging outcomes. A carefully selected battery of valid and reliable tests will be administered at age 11-12 to assess neurobehavioral development. Another unique aspect is the proposed nested study of children with high and low exposure to TRAP during early childhood to assess the physiologic impact of TRAP on the developing brain using quantitative magnetic resonance imaging (MRI). The anticipated results will address a significant gap in scientific knowledge of the potential neurotoxicity of a ubiquitous environmental exposure with far-reaching consequences for future studies and public health. PUBLIC HEALTH RELEVANCE: The association between exposure to traffic-related air pollution (TRAP) during early childhood and neurobehavioral and neuroimaging outcomes has not been thoroughly examined. The objective of the proposed study is to determine if children exposed to increased levels of TRAP during critical time periods of brain development have altered neurobehavior in childhood as measured by a battery of valid and reliable tests and to assess the physiologic impact of TRAP exposure on brain structure, organization, and function using quantitative magnetic resonance imaging (MRI). These results will fill important gaps in current scientific knowledge related to the relationship between TRAP exposure and neurobehavior and central nervous system effects.