Gray F
Laboratoire de Neuropathologie, Hôpital Raymond Poincaré, Faculté de Médecine Paris-Ouest, Garches.
Rev Neurol (Paris). 1997 Nov;153(11):629-40.
Early HIV-1 invasion of the central nervous system has been demonstrated by many cerebrospinal fluid studies; however, most HIV-1 carriers remains neurologically unimpaired during the so called "asymptomatic" period lasting from seroconversion to symptomatic AIDS. Therefore, there are very few neuropathological studies in the early pre-AIDS stages and the natural history of central nervous system changes in HIV-1 infection remains poorly understood. Examination of brains of asymptomatic HIV-1 positive individuals who died accidentally and of rare cases with acute fatal encephalopathy revealing HIV infection, and comparison with experimental simian immunodeficiency virus and feline immunodeficiency virus infections suggest that invasion of the CNS by HIV-1 occurs at the time of primary infection and induces an immunological process in the central nervous system. This includes an inflammatory T-cell reaction with vasculitis and leptomeningitis, and immune activation of brain parenchyma with increased number of microglial cells, upregulation of major histocompatibility complex class II antigens and local production of cytokines. Myelin pallor and gliosis of the white matter are usually found are likely to be the consequence of opening of the blood brain barrier due to vasculitis; direct damage to oligodendrocytes by cytokines may also interfere. These white matter changes may explain, at least partly, the early cerebral atrophy observed, by magnetic resonance imaging, in asymptomatic HIV-1 carriers. In contrast, cortical damage seems to be a late event in the course of HIV-1 infection. There is no significant neuronal loss at the early stages of the disease, no accompanying increase in glial fibrillary acid protein staining in the cortex, and only exceptional neuronal apoptosis. Although HIV-1 proviral DNA may be demonstrated in a number of brains, viral replication remains very low during the asymptomatic stage of HIV-1 infection. This makes it likely that, although opening of the blood brain barrier may facilitate viral entry into the brain, specific immune responses including both neutralising antibodies and cytotoxic T-lymphocytes, continuously inhibits viral replication at that stage.
许多脑脊液研究已证实HIV-1早期侵袭中枢神经系统；然而，大多数HIV-1携带者在从血清转化到出现症状性艾滋病的所谓“无症状”期神经系统仍未受损。因此，在艾滋病前期的早期阶段，神经病理学研究非常少，HIV-1感染中枢神经系统变化的自然史仍知之甚少。对意外死亡的无症状HIV-1阳性个体以及罕见的急性致命性脑病且显示HIV感染病例的大脑进行检查，并与实验性猿猴免疫缺陷病毒和猫免疫缺陷病毒感染进行比较，结果表明HIV-1在初次感染时就侵袭中枢神经系统，并在中枢神经系统中引发免疫过程。这包括伴有血管炎和软脑膜炎的炎症性T细胞反应，以及脑实质的免疫激活，表现为小胶质细胞数量增加、主要组织相容性复合体II类抗原上调和细胞因子的局部产生。通常发现的白质髓鞘苍白和胶质增生可能是血管炎导致血脑屏障开放的结果；细胞因子对少突胶质细胞的直接损伤也可能起作用。这些白质变化至少可以部分解释在无症状HIV-1携带者中通过磁共振成像观察到的早期脑萎缩。相比之下，皮质损伤似乎是HIV-1感染过程中的晚期事件。在疾病早期没有明显的神经元丢失，皮质中胶质纤维酸性蛋白染色没有伴随增加，只有罕见的神经元凋亡。虽然在许多大脑中可以检测到HIV-1前病毒DNA，但在HIV-1感染的无症状阶段病毒复制仍然非常低。这使得尽管血脑屏障开放可能促进病毒进入大脑，但包括中和抗体和细胞毒性T淋巴细胞在内的特异性免疫反应在该阶段持续抑制病毒复制。
