MOLECULAR NEUROIMAGING OF AIDS DEMENTIA--ANIMAL MODELS

描述（改编自摘要）：拟议的工作源于 在获得性脑梗死患者中观察神经元疾病进展 免疫缺陷综合征（艾滋病），并作为其目标的MRS的使用， 神经元损失、神经元功能障碍的非侵入性定量， 艾滋病痴呆综合征猿猴模型的脑代谢异常 （ADC）。 研究者假设，与以下类似的神经病理学事件 那些经历了艾滋病毒感染后发生感染SIV 在SIV猕猴模型中。 目前，没有简单、可靠和非侵入性的 有方法可以评估进行性神经系统疾病 与体内AIDS相关的损伤; MRS有能力提供这种 评估。 研究者建议量化神经元损伤 直接通过MRS测量SIV感染后持续的N-乙酰基 天冬氨酸（NAA），一种只存在于神经元中的分子， 监测其他大脑代谢标志物的任何变化，特别是， 具体目的是：（1） 通过质子MRS成像非侵入性地量化，区域分布， NAA和其他代谢物的变化模式和程度 SIV感染猕猴体内感染的不同阶段;（2）验证 高分辨离体脑光谱学活体测量 提取物;（3）确定细胞病理学， 通过对神经元的定量研究， 内容，突触和树突密度，和星形细胞增多;和（4） 确定病毒定位与代谢和 病理异常

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.