Early brain injury in the SIV-macaque model of AIDS
Early brain injury in the SIV-macaque model of AIDS
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DOI：
10.1097/00002030-200012220-00005
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发表时间：
2000-12-22
期刊：
影响因子：
3.8
通讯作者：
Lackner, AA
中科院分区：
文献类型：
--
作者：
González, RG;Cheng, LL;Lackner, AA
目的：明确siv -猕猴艾滋病模型感染后不久和疾病后期中枢神经系统细胞损伤的类型和严重程度。设计和方法：从三组猕猴中抽取相邻的额皮质灰质样本：未感染的对照组（n = 4）、急性组（感染后14天，n = 4）和慢性组（感染后平均2年，n = 7）。采用体外高分辨率磁共振成像技术对快速冷冻的完整组织进行体外高分辨率磁共振成像，并对福尔马林固定组织中突触素、钙结合蛋白和胶质纤维酸性蛋白（GFAP）进行定量神经病理学检测。结果：检测到n-乙酰天冬氨酸和钙结合蛋白的缺失（表明神经元损伤和/或死亡）和突触体素免疫反应性的降低（表明突触树突损伤），同时GFAP升高（表明反应性胶质细胞增生）。随着感染后时间的延长，细胞损伤逐渐加重。结论：这些结果是第一个直接证据，证明神经损伤发生在感染后不久。随着时间的推移，损伤的恶化表明中枢神经系统的早期反应与痴呆症之间存在联系，痴呆症在感染过程中发生。这种联系可能对中枢神经系统损伤的治疗方法的研究和发展具有广泛的意义。
Objective: To specify the type and severity of cellular damage in the central nervous system soon after infection and at later stages of disease in the SIV-macaque model of AIDS.Design and methods: Adjacent samples of frontal cortical gray matter were taken from three groups of macaques: uninfected controls (n = 4), acute (14 days post-infection; n = 4), and chronic (mean 2 years post-infection; n = 7). In vitro high resolution magnetic resonance spectroscopy of snap frozen intact tissue and quantitative neuropathology measurements of synaptophysin, calbindin, and glial fibrillary acidic protein (GFAP) in formalin-fixed tissue were performed.Results: Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis). Cellular injury worsened progressively with increased time after infection.Conclusions: These results are the first direct evidence that neuronal injury occurs soon after infection. The exacerbation of injury with time suggests a connection between the early response of the central nervous system and dementia, which occurs fate in the course of infection. This connection may have broad implications for the study of and the development of therapies for damage of the central nervous system by (C) 2000 Lippincott Williams & Wilkins.