MR SPECTROSCOPY IN THE SIV INFECTED MACAQUE MODEL OF NEUROAIDS

感染 SIV 的神经艾滋病猕猴模型中的 MR 光谱

• 批准号: 8172805
• 负责人: RAMON GILBERTO GONZALEZ
• 金额: $ 6.58万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172805
• 关键词: AIDS neuropathy; Acquired Immunodeficiency Syndrome; Animals; Antibiotics; Bone Marrow; CD8-Positive T-Lymphocytes; Cerebrum; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Event; Funding; Goals; Grant; HIV Infections; Highly Active Antiretroviral Therapy; Injury; Institution; Lead; Macaca; Macaca mulatta; Magnetic Resonance; Measurement; Minocycline; Modeling; Monkeys; Neurocognitive; Neuronal Injury; Neurons; Pathogenesis; Pathway interactions; Patients; Phagocytes; Recovery; Research; Research Personnel; Resources; SIV encephalitis; Source; Spectrum Analysis; Testing; United States National Institutes of Health; antiretroviral therapy; macrophage; monocyte; nervous system disorder; theories; trafficking

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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AIDS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并活化，然后进入CNS，在那里它变成血管周围的巨噬细胞，引发导致神经元损伤的级联事件。 我们试图了解单核吞噬细胞（MP）的运输，MP营业额在中枢神经系统和神经元的恢复动力学。 此外，尽管进行了高效抗逆转录病毒治疗（HAART），但累积性神经系统疾病的持续存在导致了对预防性治疗的探索。 最近，米诺环素，一种耐受性良好，价格低廉的抗生素，已被测试用于各种神经元疾病，包括NeuroAIDS。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。我们研究的目的是阐明米诺环素的作用机制。 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收集的数据来实现。为此，我们正在利用SIV感染的、CD 8 + T淋巴细胞耗尽的猕猴模型（SIV+/CD 8-），其通常导致可靠的神经AIDS加速模型，因为95%的持续（长期）耗尽的动物表现出SIV脑炎的组织病理学体征。