MR Spectroscopy of SIV Brain Injury

描述（由申请人提供）：关于神经艾滋病发病机制的主要理论是，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巨噬细胞，并引发一系列事件，导致神经元损伤。根据我们实验室进行的实验，我们扩展了这一理论，并提出神经艾滋病中神经元损伤的积累需要被感染/激活的cd14 /16单核吞噬细胞（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。

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.