Podell M, Maruyama K, Smith M, Hayes K A, Buck W R, Ruehlmann D S, Mathes L E
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus 43210, USA.
J Acquir Immune Defic Syndr. 1999 Sep 1;22(1):10-8. doi: 10.1097/00042560-199909010-00002.
Six cats infected intravenously at 8 weeks of age with feline immunodeficiency virus Maryland isolate (FIV-MD), were evaluated at 8 and 14 months of age (6 months and 12 months postinfection, respectively) with high spatial resolution proton magnetic resonance spectroscopy (MRS) of the frontal cortex. Two separate control cat groups were evaluated at 8 months and 16 months of age. Single voxel two-dimensional high-resolution proton magnetic resonance imaging was performed using the PRESS sequence by selecting a 0.125 ml volume of interest in the medial frontal cortex. A significant reduction in both N-acetylaspartate (NAA) and NAA: choline ratio was found in the FIV 14-month-old group compared with FIV 8-month-old cats, and to the respective age-matched control 16-month-old cats. A negative correlation between NAA and CD4 lymphocyte count was seen in the FIV-14 group only. This group of FIV cats also exhibited a higher proportion of quantitative electroencephalographic relative slow wave activity (RSWA) that correlated to lower NAA content in the frontal cortical voxel. Although peripheral blood proviral load increased over time of infection, no correlation was found between proviral blood or lymph node load and NAA values, CD4 lymphocyte counts, or frontal cortical RSWA. Thus, this study demonstrated that neurologic functional disruption of the frontal cortex correlated strongly with neuronal injury and/or loss in FIV-MD-infected cats independent of peripheral proviral load. The ability to define in vivo neurodegeneration further in this animal model helps in understanding the neuropathogenesis of lentivirus infection, and possibly, a means to follow progression and reversibility during the initial stages of brain infection as therapeutic agents are identified.
6只8周龄时经静脉感染猫免疫缺陷病毒马里兰分离株(FIV-MD)的猫,在8个月和14个月龄时(分别为感染后6个月和12个月)接受了额叶皮质的高空间分辨率质子磁共振波谱(MRS)评估。两个单独的对照猫组分别在8个月和16个月龄时进行了评估。使用PRESS序列,通过在内侧额叶皮质中选择0.125 ml的感兴趣体积,进行了单体素二维高分辨率质子磁共振成像。与8个月龄的FIV猫以及各自年龄匹配的16个月龄对照猫相比,14个月龄的FIV组中N-乙酰天门冬氨酸(NAA)和NAA:胆碱比值均显著降低。仅在FIV-14组中观察到NAA与CD4淋巴细胞计数之间呈负相关。这组FIV猫还表现出更高比例的定量脑电图相对慢波活动(RSWA),其与额叶皮质体素中较低的NAA含量相关。尽管外周血前病毒载量随感染时间增加,但未发现前病毒血液或淋巴结载量与NAA值、CD4淋巴细胞计数或额叶皮质RSWA之间存在相关性。因此,本研究表明,额叶皮质的神经功能破坏与FIV-MD感染猫的神经元损伤和/或丢失密切相关,与外周前病毒载量无关。在该动物模型中进一步定义体内神经退行性变的能力有助于理解慢病毒感染的神经发病机制,并且可能有助于在确定治疗药物时追踪脑感染初始阶段的进展和可逆性。