MOLECULAR NEUROIMAGING OF AIDS DEMENTIA--ANIMAL MODELS

描述(改编自摘要)：拟议的工作源于 获得性视网膜炎患者神经元性疾病进展的观察 免疫缺陷综合征(AIDS)，其目标是使用MRS治疗 无创性量化神经元丢失、神经元功能障碍和 艾滋病痴呆复合体的猿类模型的脑代谢异常 (ADC)。调查者假设类似于 HIV感染后的经历发生在感染SIV之后 在SIV猕猴模型中。目前，没有简单、可靠和非侵入性的 评估进展性神经病的方法是可用的。 体内与艾滋病相关的损伤；MRS有能力提供这种 评估。研究人员建议将神经元损伤量化 直接测量N-乙酰在SIV感染后的持续时间 天冬氨酸(NAA)，一种专门存在于神经元中的分子，并 监测其他大脑代谢标志物的任何变化，特别是， 含有胆碱的代谢物，由MRS具体目的是：(1) 通过质子磁共振成像无创性地量化，区域分布， 体内NAA和其他代谢物的变化模式和程度 体内感染SIV的猕猴感染不同阶段；(2)验证 高分辨率体外脑光谱在体测量中的应用 同一动物的提取物；(3)确定细胞病理学 通过对神经元的定量研究来支持这些代谢变化 内容物、突触和树突密度以及星形细胞增多；以及(4) 确定病毒定位与代谢和 病理性异常。

DESCRIPTION (adapted from the Abstract): The proposed work derives from observations of neuronal disease progression in people with the acquired immunodeficiency syndrome (AIDS), and has as its goal the use of MRS for the non-invasive quantification of neuronal loss, neuronal dysfunction, and brain metabolic abnormalities in a simian model of the AIDS dementia complex (ADC). The Investigator postulates that neuropathological events similar to those experienced after HIV infection occur subsequent to infection with SIV in the SIV macaque model. Currently, no simple, reliable, and non-invasive methods are available with which to assess the progressive neurological injury associated with AIDS in vivo; MRS has the capability to provide such assessments. The Investigator proposes to quantify the neuronal injury sustained after SIV infection directly through MRS measurements of N-acetyl aspartate (NAA), a molecule which resides exclusively in neurons, and to monitor any variation in other brain metabolic markers, in particular, choline containing metabolites, by MRS. The specific aims are: (1) to quantify noninvasively by proton MRS imaging, the regional distribution, pattern and extent of changes in NAA and other metabolites in the SIV-infected macaque in vivo at different stages of infection; (2) to verify the in vivo measurements by high resolution in vitro spectroscopy of brain extracts from the same animal; (3) to determine the cellular pathology that underlie these metabolic alterations by quantitative studies of neuronal content, synaptic and dendritic density, and astrocytosis; and (4) to determine the relationship of viral localization to the metabolic and pathological abnormalities.