Avgeropoulos N, Kelley B, Middaugh L, Arrigo S, Persidsky Y, Gendelman H E, Tyor W R
Department of Neurology, Medical University of South Carolina, Charleston 29425, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 May 1;18(1):13-20. doi: 10.1097/00042560-199805010-00003.
Severe combined immunodeficient (SCID) mice inoculated intracerebrally (i.c.) with HIV-infected human monocytes develop brain pathology similar to that in humans with HIV encephalitis. This includes HIV-positive macrophages and multinucleated giant cells, astrogliosis, microglial nodules, and neuronal dropout. These xenografts survive about 1 month. To develop a model of chronic HIV encephalitis and to assay the resulting behavioral abnormalities, we reinoculated SCID mice i.c. every 4 weeks for 3 months with either HIV-infected human monocytes (n = 5) or uninfected human macrophages (n = 4) or administered no inoculation (n = 6); these three groups were monitored for behavioral abnormalities. Tests of cognitive function in a Morris water maze 3.5 months after the first inoculation suggested that HIV-infected mice performed poorly compared with controls. Following testing in the water maze on days 4 and 5 of acquisition, motor activity of infected mice was reduced in comparison with that of controls. Retention of goal location when tested 1 week later was impaired in HIV-infected mice compared with controls. Histopathologic analysis of brains revealed significant astrogliosis and strongly suggested higher numbers of major histocompatibility complex (MHC) class II-positive multinucleated macrophages in HIV-infected compared with control mice. Thus, our preliminary studies indicate that SCID mice with HIV encephalitis develop behavioral abnormalities reminiscent of human disease. These behavioral abnormalities are associated with significantly increased astrogliosis, the presence of HIV, and probably multinucleated giant cells. These studies further support the use of this SCID animal model system for studies of the pathogenesis of HIV encephalitis and for drug interventions.
将感染HIV的人类单核细胞脑内接种到严重联合免疫缺陷（SCID）小鼠体内，会使其出现与人类HIV脑炎相似的脑部病变。这包括HIV阳性巨噬细胞和多核巨细胞、星形胶质细胞增生、小胶质结节以及神经元脱失。这些异种移植可存活约1个月。为建立慢性HIV脑炎模型并检测由此产生的行为异常，我们每4周对SCID小鼠进行一次脑内再接种，持续3个月，一组接种感染HIV的人类单核细胞（n = 5），一组接种未感染的人类巨噬细胞（n = 4），另一组不进行接种（n = 6）；对这三组小鼠的行为异常进行监测。首次接种3.5个月后在莫里斯水迷宫中进行认知功能测试，结果显示感染HIV的小鼠与对照组相比表现较差。在习得阶段的第4天和第5天进行水迷宫测试后，感染小鼠的运动活动与对照组相比有所减少。与对照组相比，感染HIV的小鼠在1周后测试时对目标位置的记忆受损。对大脑进行组织病理学分析发现有显著的星形胶质细胞增生，并且强烈提示与对照小鼠相比，感染HIV的小鼠中主要组织相容性复合体（MHC）II类阳性多核巨噬细胞数量更多。因此，我们的初步研究表明，患有HIV脑炎的SCID小鼠会出现类似于人类疾病的行为异常。这些行为异常与星形胶质细胞增生显著增加、HIV的存在以及可能的多核巨细胞有关。这些研究进一步支持了使用这种SCID动物模型系统来研究HIV脑炎的发病机制以及进行药物干预。
