METABOLIC RESPONSES TO SIV INFECTION REVEALED BY IN VIVO ^1H MR SPECTROSCOPY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。对HIV感染者进行的活体^1H磁共振波谱（MRS）研究显示，不同脑区存在显著的代谢异常，但对这些异常的了解还很有限。本文用活体氢质子磁共振波谱（1H-MRS）研究了15只SIV感染猕猴在感染后第一个月内额叶皮质、基底节和白色物质的代谢变化。在感染后2周（p.i.）病毒血症峰值时观察到最显著的异常。N-乙酰天冬氨酸（NAA），胆碱（Cho）和肌醇（MI）共振的变化被发现相对于肌酸（Cr）共振和绝对值。Cho和Cho/Cr的变化在整个大脑区域中最相似，在注射后2周增加，并且在4周时下降到基线水平以下。随着时间的推移，观察到MI/Cr比值的复杂区域变化。最有趣的是NAA的区域差异。NAA和NAA/Cr的显着下降，反映神经元损伤，只观察到在病毒血症高峰期的时间在额叶皮层。虽然有几种潜在的机制来解释这些结果，但这些数据最好地支持了这样一种假设，即不同的大脑区域对艾滋病病毒引起的神经元损伤具有不同的内在脆弱性。

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. In vivo ^1H magnetic resonance spectroscopy (MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region and are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 15 SIV-infected macaques were investigated using in vivo 1H MRS during the first month of infection. The most significant abnormalities were observed at the time of peak viremia, at 2 weeks post infection (p.i.). Changes in the N-acetylaspartate (NAA), ¿choline¿ (Cho) and myo-inositol (MI) resonances were found relative to the creatine (Cr) resonance and in absolute terms. Changes in Cho and Cho/Cr were most similar across the brain regions, increasing at 2 weeks p.i., and falling below baseline levels at 4 weeks. Complex regional variations in MI/Cr ratios were observed over time. Most interesting were the regional differences in NAA. Significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex at the time of peak viremia. While there are several potential mechanisms to explain these results, the data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.