Department of Neurology, Emory University School of Medicine, Decatur, GA 30033, USA.
Neurochem Res. 2012 Dec;37(12):2836-41. doi: 10.1007/s11064-012-0877-z. Epub 2012 Sep 11.
HIV encephalitis (HIVE) is often complicated by opiate abuse. Based on human pathological, animal and in vitro studies, opiates are thought to exacerbate HIVE. To test this hypothesis we exposed 10 week old SCID mice with HIVE to morphine and examined histopathological parameters. Mice inoculated intracerebrally with either HIV-infected or uninfected (control mice) human macrophages were immediately implanted subcutaneously with pellets containing saline, morphine or morphine plus naltrexone. They were sacrificed after 10 days. Immunostaining for astrocytes (GFAP), mouse mononuclear phagocytes (CD45) and neuronal dendrites (MAP2) was analyzed by densitometry. HIVE mice exposed to either saline, morphine or morphine plus naltrexone also had brain sections counted for HIV+ human macrophages. Typical HIVE pathology was present, consistent with previously published studies. Surprisingly, there were no effects on astrogliosis, microgliosis and MAP2 decreases in the HIVE, morphine treated group. There was also no effect of morphine exposure on numbers of p24+ human macrophages. These results emphasize the complexities of modeling opiate effects in HIVE and the potential significance of opiate abuse on HIVE in humans.
HIV 脑炎(HIVE)常伴有阿片类药物滥用。基于人体病理学、动物和体外研究,阿片类药物被认为会加重 HIVE。为了验证这一假说,我们将患有 HIVE 的 10 周龄 SCID 小鼠暴露于吗啡,并检查组织病理学参数。将感染或未感染 HIV 的(对照小鼠)人类巨噬细胞脑内接种的小鼠立即皮下植入含有生理盐水、吗啡或吗啡加纳曲酮的丸剂。10 天后处死它们。通过密度测定法分析星形胶质细胞(GFAP)、小鼠单核吞噬细胞(CD45)和神经元树突(MAP2)的免疫染色。还对暴露于生理盐水、吗啡或吗啡加纳曲酮的 HIVE 小鼠的脑切片进行了 HIV+人类巨噬细胞计数。存在典型的 HIVE 病理学,与之前发表的研究一致。令人惊讶的是,在 HIVE 中,吗啡处理组的星形胶质细胞增生、小胶质细胞增生和 MAP2 减少没有任何影响。吗啡暴露对 p24+人类巨噬细胞数量也没有影响。这些结果强调了在 HIVE 中模拟阿片类药物作用的复杂性,以及阿片类药物滥用对人类 HIVE 的潜在意义。