Bagasra O, Bobroski L, Sarker A, Bagasra A, Saikumari P, Pomerantz R J
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
J Neurovirol. 1997 Apr;3(2):153-67. doi: 10.3109/13550289709015805.
A majority of human immunodeficiency virus type I (HIV-1)-infected-individuals manifest a plethora of central nervous system (CNS) diseases unrelated to opportunistic infections, including acquired immune deficiency syndrome (AIDS)-dementia complex (ADC), encephalitis, and various other disorders of the CNS. A series of devastating clinical conditions in the CNS of certain HIV-1-infected-individuals may be caused by infection of cells in the brain parenchyma. ADC is characterized by cognitive dysfunction, motor difficulties, coordination abnormalities and other neurological signs and symptoms, which develop in many HIV-1-infected-individuals. The precise molecular mechanisms leading to AIDS dementia remain incompletely explained. Various mechanisms including cytokine dysregulation, toxic effects of viral proteins and release of certain toxic substances from macrophages, especially nitric oxide, have been implicated as pathogenic mediators in the development of ADC. We have examined post mortem CNS tissues collected from 22 patients, previously diagnosed with AIDS, to explore if nitric oxide is responsible for the observed pathology in ADC. As controls, we utilized tissues collected from the brains of patients who expired without AIDS or other CNS pathologies. In addition, we also utilized post-mortem brain tissues from eight patients who were diagnosed with multiple sclerosis (MS) and were found to express inducible nitric oxide synthase (iNOS) in our previous studies, as positive controls. Highly sensitive in situ reverse transcriptase-initiated polymerase chain reaction (RT-IS-PCR) studies demonstrated that iNOS mRNA was present in the CNS tissues from all the positive MS controls, but were absent in all 22 specimens from AIDS patients, as well as in the brain tissues from normal controls. We have also analyzed the tissues for the presence of the NO reaction product, nitrotyrosine, to evaluate the presence of a protein nitrosalation adduct. Nitrotyrosine was not demonstrable in any of the AIDS brains. These findings indicate that iNOS may not play a significant role in the neuropathogenesis of most cases of ADC.
大多数感染I型人类免疫缺陷病毒（HIV-1）的个体表现出大量与机会性感染无关的中枢神经系统（CNS）疾病，包括获得性免疫缺陷综合征（AIDS）痴呆综合征（ADC）、脑炎以及CNS的各种其他病症。某些感染HIV-1的个体CNS中一系列具有破坏性的临床病症可能是由脑实质细胞感染引起的。ADC的特征为认知功能障碍、运动困难、协调异常以及其他神经体征和症状，在许多感染HIV-1的个体中都会出现。导致AIDS痴呆的确切分子机制仍未完全阐明。包括细胞因子失调、病毒蛋白的毒性作用以及巨噬细胞释放某些有毒物质（尤其是一氧化氮）等多种机制，已被认为是ADC发病过程中的致病介质。我们检查了从22例先前被诊断为AIDS的患者身上采集的死后CNS组织，以探究一氧化氮是否是ADC中观察到的病理变化的原因。作为对照，我们使用了从无AIDS或其他CNS病变而死亡的患者大脑中采集的组织。此外，我们还使用了8例被诊断为多发性硬化症（MS）且在我们先前研究中发现表达诱导型一氧化氮合酶（iNOS）的患者的死后脑组织作为阳性对照。高灵敏度原位逆转录引发聚合酶链反应（RT-IS-PCR）研究表明，所有阳性MS对照的CNS组织中均存在iNOS mRNA，但在所有22例AIDS患者的标本以及正常对照的脑组织中均未检测到。我们还分析了组织中是否存在NO反应产物硝基酪氨酸，以评估蛋白质亚硝化加合物的存在情况。在任何AIDS患者的大脑中均未检测到硝基酪氨酸。这些发现表明，iNOS在大多数ADC病例的神经发病机制中可能不起重要作用。
