MR-Based Study of Hypomyelination by Lead Poisoning

基于磁共振的铅中毒髓鞘形成低下研究

• 批准号: 7107978
• 负责人: SUSUMU MORI
• 金额: $ 31.29万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107978
• 关键词: developmental neurobiology; electron microscopy; histology; laboratory rat; lead poisoning; magnetic resonance imaging; myelination; myelinopathy; neurotoxicology; neurotoxins; newborn animals; three dimensional imaging /topography

DESCRIPTION (provided by applicant): The overall goal of this project is to establish the usefulness of magnetic resonance microimaging as a tool to study myelination toxicology and apply it to investigate hypomyelination caused by lead poisoning. Myelination is a very complex process; myelination starts at the different time point with different rates for each white matter tract. As a result, comprehensive characterization of myelination status, even of the normal state, is not a straightforward task. This poses a great challenge for toxicological assessment of myelination. In this project, we will use the ex vivo high-resolution MRI and a rat neonate model to characterize the temporal and spatial profile of the myelination process. Using this technique following three aims will be pursued. Aim 1: Characterization of temporal and spatial profile of the normal rat myelination process using MRI and fixed brain samples. Hypothesis: "Ex vivo high-resolution MRI can reveal the dynamic process of myelination three-dimensionally in a tract-by-tract basis". The microimaging technique will be applied to a series of normal brain samples at different development stages to monitor the myelination process. The observed changes of MR parameters will be correlated with histology to confirm the hypothesis. Aim 2: Study of the myelination abnormality by high-dose lead administration. Hypothesis: "Ex vivo high-resolution MRI can sensitively and efficiently detect myelination abnormalities" Hypomyelination by lead uptake has been previously reported and our preliminary data show that MRI can sensitively detect the hypomyelination of specific white matter tracts. We will use this system to compare MRI findings and histology data and to validate the hypothesis. Aim 3: Study of the temporal, spatial, and dose profiles of the myelination abnormality by low-dose lead administration. Hypothesis: "Low-dose lead uptake induces the myelination abnormality, which is independent of malnutrition". Hypomyelination by lead uptake has been considered as one of the important developmental impairments by the lead uptake. However, to date, it has not been clear whether the observed hypomyelination is secondary to the concomitant malnutrition and weight loss. Using the MRI-based technique and normative database established under Aim 1 and 2, we will perform comprehensive myelination studies to examine the hypothesis

描述（由申请人提供）：本项目的总体目标是建立磁共振显微成像作为研究髓鞘形成毒理学的工具的有用性，并将其应用于研究铅中毒引起的髓鞘形成不足。髓鞘形成是一个非常复杂的过程;髓鞘形成在不同的时间点开始，对于每个白色物质束具有不同的速率。因此，髓鞘形成状态的全面表征，即使是正常状态，也不是一个简单的任务。这对髓鞘形成的毒理学评估提出了巨大的挑战。在这个项目中，我们将使用离体高分辨率MRI和新生大鼠模型来表征髓鞘形成过程的时间和空间分布。使用这种技术将追求以下三个目标。 目的1：利用MRI和固定的脑组织标本对正常大鼠髓鞘形成过程的时间和空间分布进行表征。假设：“离体高分辨率MRI可以在逐束的基础上三维地揭示髓鞘形成的动态过程”。显微成像技术将应用于一系列不同发育阶段的正常大脑样本，以监测髓鞘形成过程。将观察到的MR参数变化与组织学相关联，以证实假设。 目的二：研究大剂量铅致髓鞘形成异常。假设：“离体高分辨率MRI可以灵敏和有效地检测髓鞘形成异常”之前已经报道了铅摄取导致的髓鞘形成不足，我们的初步数据显示，MRI可以灵敏地检测特定白色物质束的髓鞘形成不足。我们将使用这个系统来比较MRI结果和组织学数据，并验证假设。 目的3：研究低剂量铅致髓鞘形成异常的时间、空间和剂量分布。假设：“低剂量铅摄入导致髓鞘形成异常，这与营养不良无关”。铅摄入引起的髓鞘形成不足被认为是铅摄入引起的重要发育障碍之一。然而，迄今为止，尚不清楚所观察到的髓鞘形成不足是否继发于伴随的营养不良和体重减轻。我们将使用基于MRI的技术和根据目标1和目标2建立的标准数据库，进行全面的髓鞘形成研究，以检验这一假设