MR Spectroscopy of SIV Brain Injury

SIV 脑损伤的磁共振波谱分析

• 批准号: 6948415
• 负责人: RAMON GILBERTO GONZALEZ
• 金额: $ 72.7万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6948415
• 关键词: AIDS therapy; CD14 molecule; CD16 molecule; Macaca mulatta; brain imaging /visualization /scanning; brain injury; cell migration; cytotoxic T lymphocyte; immunocytochemistry; nuclear magnetic resonance spectroscopy; phagocytes; simian immunodeficiency virus

DESCRIPTION (PROVIDED BY APPLICANT): A leading theory for the pathogenesis of neuroAIDS is that a specific bone marrow derived blood monocyte is virally infected and activated, then traffics into the CNS where it becomes a perivascular macrophage and sets off a cascade of events that result in neuronal injury. In light of experiments performed in our laboratory, we extend this theory and propose that accumulation of neuronal injury in neuroAIDS requires continuous trafficking of infected/activated CD 14/16 monocytic phagocytes (MPs) into the CNS to surmount turnover of these cells and endogenous neuronal recovery mechanisms. We seek to understand the dynamics of MP trafficking, MP turnover in the CNS and neuronal recovery through an experimental design that tests a series of specific hypotheses derived from the central theory. We will use 1H magnetic resonance spectroscopy (MRS) at high field (7T) in an accelerated simian immunodeficiency virus (SIV) macaque model of neuroAIDS that reliably produces SIV encephalitis and neuronal injury within weeks. Moreover, we will use HAART to experimentally manipulate CNS trafficking of activated blood monocytes, and modulate neuronal injury. Simultaneously with imaging, we will quantify levels of activated (CD14+/CD16+) monocytes, their SPV DNA and RNA levels, and virus in blood. We will complete this study with detailed immunological, virological, neuropathologic and MRS studies of the brains of the same animals. Our specific aims are: Specific Aim 1. Determine the amount of virally infected/activated CD14/16 MPs in blood, and at the same time determine regional neuronal injury in SIV infected/CD8 depleted macaques and similar animals undergoing HAART. Specific Aim 2. Determine the severity of CNS injury by in vivo & ex vivo MRS and immunohistochemistry in different brain regions, and determine the levels of perivascular MPs in those regions.

描述(申请人提供)：神经艾滋病发病机制的一个主要理论是，特定的骨髓来源的血液单核细胞被病毒感染和激活，然后进入中枢神经系统，在那里它成为血管周围的巨噬细胞，并引发一系列导致神经元损伤的事件。根据我们实验室的实验，我们扩展了这一理论，并提出神经艾滋病神经元损伤的积累需要感染/激活的CD14/16单核细胞吞噬细胞(MPS)持续运输到中枢神经系统，以克服这些细胞的周转和内源性神经元恢复机制。 我们试图通过一个实验设计来测试一系列源自中心理论的特定假设，以了解MP运输、MP在中枢神经系统中的周转和神经元恢复的动力学。我们将在高场(7T)下使用1H磁共振波谱(MRS)在神经艾滋病的加速猴免疫缺陷病毒(SIV)猕猴模型中使用，该模型可在几周内可靠地产生SIV脑炎和神经元损伤。此外，我们将使用HAART来实验性地操纵中枢神经系统对激活的血液单核细胞的运输，并调节神经元损伤。在成像的同时，我们将量化激活的(CD14+/CD16+)单核细胞水平，它们的SPVDNA和RNA水平，以及血液中的病毒。我们将通过对相同动物的大脑进行详细的免疫学、病毒学、神经病理学和MRS研究来完成这项研究。我们的具体目标是： 具体目的1.检测SIV感染/CD8缺失猕猴及类似动物接受HAART后血液中CD14/16MPS的含量，同时检测局部神经元损伤。 具体目的2.通过体内外MRS和免疫组织化学方法检测不同脑区中枢神经系统损伤的严重程度，并测定这些脑区血管周围MPS水平。