Marcario J K, Manaye K F, SantaCruz K S, Mouton P R, Berman N E J, Cheney P D
Departments of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7185, USA.
J Neurovirol. 2004 Dec;10(6):387-99. doi: 10.1080/13550280490521131.
Infection with human immunodeficiency virus-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS) in humans, causes a spectrum of neuropathology that includes alterations in behavior, changes in evoked potentials, and neuronal degeneration. In the simian immunodeficiency virus (SIV) model of HIV infection, affected monkeys show clinical symptoms and neurological complications that mimic those observed in human neuro-AIDS. To investigate the relationship between morphological correlates and neurophysiological deficits, unbiased stereology was used to assess total neuron number, volume, and neuronal density for all neurons in the globus pallidus (GP) and for dopamine (DA)-containing neurons in the substantia nigra (SN) in eight macaques inoculated with macrophage-tropic, neurovirulent SIV (SIVmac R71/17E), and five control animals. There was a significant difference between rapid progressors and controls for both neuron number (P < .01) and neuronal density (P < .05) in the GP, and for neuron number (P < .05) in the SN. Neuron loss ranged from 6% to 70% in the GP and from 10% to 50% in the SN. Neuropathological analyses confirmed neuroAIDS-like changes in brain, including microglial nodules, extensive perivascular cuffing and/or the presence of multinucleated giant cells, and alterations in neuronal morphology in the majority of the rapid progressors. By comparison, slow progressors showed little, if any, neuropathology. These neuropathological changes in SIV-infected monkeys indicate that neuron death and morphological alterations in the basal ganglia may contribute to the motor impairments reported in the SIV model and, by analogy, in the subset of patients afflicted with motor impairment in human neuro-AIDS.
人类免疫缺陷病毒1型（HIV-1）是人类获得性免疫缺陷综合征（AIDS）的病原体，可引发一系列神经病理学变化，包括行为改变、诱发电位变化和神经元变性。在HIV感染的猴免疫缺陷病毒（SIV）模型中，受感染的猴子会出现类似于人类神经艾滋病中观察到的临床症状和神经并发症。为了研究形态学相关性与神经生理缺陷之间的关系，采用无偏倚立体学方法评估了8只接种嗜巨噬细胞、神经毒性SIV（SIVmac R71/17E）的猕猴以及5只对照动物苍白球（GP）中所有神经元的总数、体积和神经元密度，以及黑质（SN）中含多巴胺（DA）神经元的情况。快速进展者与对照组相比，GP中的神经元数量（P <.01）和神经元密度（P <.05）以及SN中的神经元数量（P <.05）均存在显著差异。GP中的神经元损失率为6%至70%，SN中的为10%至50%。神经病理学分析证实，大多数快速进展者的大脑出现了类似神经艾滋病的变化，包括小胶质结节、广泛的血管周围套叠和/或多核巨细胞的存在以及神经元形态改变。相比之下，缓慢进展者几乎没有神经病理学变化。SIV感染猴子的这些神经病理学变化表明，基底神经节中的神经元死亡和形态改变可能导致SIV模型中报告的运动障碍，同理，也可能导致人类神经艾滋病中患有运动障碍的部分患者出现运动障碍。
