Tracey I, Lane J, Chang I, Navia B, Lackner A, González R G
NMR Center and Neuroradiology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1997 May 1;15(1):21-7. doi: 10.1097/00042560-199705010-00004.
Infection with human immunodeficiency virus (HIV) commonly results in neurologic disease called the AIDS dementia complex. Neuronal loss and injury have been found in the HIV brain, but the underlying mechanisms are not understood. The simian immunodeficiency virus (SIV)-infected macaque is an excellent animal model for HIV infection, but neuronal loss has not been demonstrated. To determine whether neuronal damage occurs in the SIV brain, we quantified the neuronal marker N-acetylaspartate (NAA) using proton magnetic resonance spectroscopy (1H-MRS) in brain extracts of control and SIV-infected macaques and correlated these findings with histologic analyses. We found reduced NAA in the SIV-infected animals compared with controls (2.94 +/- 1.37 versus 6.21 +/- 1.73 micromol/g of wet weight; p = 0.004). A significant decrease in NAA was also found in SIV-infected animals sacrificed in the acute stages of infection 9 or 10 days after inoculation with SIVmacYnef. We conclude that SIV infection of rhesus macaques results in neuronal damage that is demonstrable shortly after infection and that 1H-MRS may be used to measure such injury. The results further support the SIV macaque as a useful model to study the mechanisms of neuropathogenesis by HIV.
人类免疫缺陷病毒（HIV）感染通常会导致一种名为艾滋病痴呆综合征的神经疾病。在HIV感染的大脑中已发现神经元丢失和损伤，但其潜在机制尚不清楚。感染猿猴免疫缺陷病毒（SIV）的猕猴是HIV感染的一种优秀动物模型，但尚未证实存在神经元丢失。为了确定SIV感染的大脑中是否发生神经元损伤，我们使用质子磁共振波谱（1H-MRS）对对照猕猴和SIV感染猕猴的脑提取物中的神经元标志物N-乙酰天门冬氨酸（NAA）进行了定量，并将这些结果与组织学分析相关联。我们发现，与对照相比，SIV感染的动物中NAA减少（湿重分别为2.94±1.37与6.21±1.73微摩尔/克；p = 0.004）。在接种SIVmacYnef后9或10天处于感染急性期时处死的SIV感染动物中，也发现NAA显著降低。我们得出结论，恒河猴感染SIV会导致感染后不久即可证实的神经元损伤，并且1H-MRS可用于测量此类损伤。这些结果进一步支持SIV猕猴作为研究HIV神经发病机制的有用模型。
