MR SPECTROSCOPY IN THE SIV INFECTED MACAQUE MODEL OF NEUROAIDS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的目标是阐明HIV感染导致脑损伤的途径。如果没有有效的抗逆转录病毒疗法(ART)治疗，大约三分之一的艾滋病患者将患有神经艾滋病。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，引发一系列导致神经元损伤的事件。我们试图了解单核细胞吞噬细胞(MP)在中枢神经系统的转运、MP周转和神经元恢复的动力学。此外，尽管进行了高效的抗逆转录病毒治疗(HAART)，但累积性神经疾病的持续存在导致了对辅助治疗的探索。最近，米诺环素，一种耐受性良好的廉价抗生素，已经在包括神经艾滋病在内的各种神经疾病上进行了测试。然而，米诺环素对HIV相关神经认知障碍(HAND)的作用机制仍不清楚。本研究旨在揭示米诺环素(S)的作用机制。这两个目标将通过评估从SIV感染的恒河猴的免疫学、免疫组织化学、病理学和磁共振光谱测量中收集的数据来实现。为此，我们利用了SIV感染的CD8+T淋巴细胞耗尽猕猴模型(SIV+/CD8-)，该模型通常会导致可靠的加速神经艾滋病模型，因为95%的持续(长期)耗尽的动物显示出SIV脑炎的组织病理学迹象。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goal is to elucidate the pathways that lead to cerebral injury by HIV infection. Without effective antiretroviral therapy (ART) treatment, approximately one third of AIDS patients will suffer from NeuroAIDS. 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, setting off a cascade of events that result in neuronal injury. We seek to understand the dynamics of monocytic phagocyte (MP) trafficking, MP turnover in the CNS and neuronal recovery. Moreover, the persistence of cumulative neurological disease despite highly active antiretroviral therapy (HAART) has led to a search for adjunctive therapies. Recently, minocycline, a well-tolerated, inexpensive antibiotic has been tested on a variety of neuronal diseases, including NeuroAIDS. However, minocycline's mechanism of action towards HIV-associated neurocognitive disorders (HAND) remains unclear. The goal of our study is to unravel minocycline's mechanism(s) of action. Both goals will be accomplished by evaluating data collected from immunological, immunohistochemical, pathological, and magnetic resonance spectroscopic measurements of SIV-infected rhesus macaque monkeys. To this end we are utilizing the SIV-infected, CD8+ T lymphocyte-depleted macaque model (SIV+/CD8-) which typically results in a reliable accelerated model of neuroAIDS, as 95 percent of persistently (long-term) depleted animals demonstrate histopathological signs of SIV encephalitis.