Despite combined antiretroviral therapy (cART), HIV infection in the CNS persists with reported increases in activation of macrophages (MΦ), microglia, and surrounding astrocytes/neurons, conferring HIV-induced inflammation. Chronic inflammation results in HIV-associated neurocognitive disorders (HAND) with reported occurrence of up to half of individuals with HIV infection. The existing HAND mouse model used by laboratories including ours, and the effect of novel agents on its pathology present with labor-intensive and time-consuming limitations since brain sections and immunohistochemistry assays have to be performed and analyzed. A novel flow cytometry-based system to objectively quantify phenotypic effects of HIV using a SCID mouse HAND model was developed which demonstrated that the HIV-infected mice had significant increases in astrogliosis, loss of neuronal dendritic marker, activation of murine microglia, and human macrophage explants compared to uninfected control mice. HIV p24 could also be quantified in the brains of the infected mice. Correlation of these impairments with HIV-induced brain inflammation and previous behavioral abnormalities studies in mice suggests that this model can be used as a fast and relevant throughput methodology to quantify preclinical testing of novel treatments for HAND.

尽管采用联合抗逆转录病毒疗法 (cART)，但 CNS 中的 HIV 感染仍然存在，据报道巨噬细胞 (MΦ)、小胶质细胞和周围星形胶质细胞/神经元的活化增加，从而导致 HIV 诱导的炎症。慢性炎症会导致 HIV 相关的神经认知障碍 (HAND)，据报道，多达一半的 HIV 感染者会发生这种情况。包括我们在内的实验室使用的现有 HAND 小鼠模型以及新型药物对其病理学的影响存在劳动密集型和耗时的限制，因为必须执行和分析脑切片和免疫组织化学测定。开发了一种基于流式细胞术的新型系统，可使用 SCID 小鼠 HAND 模型客观量化 HIV 的表型效应，该系统证明 HIV 感染的小鼠星形胶质细胞增生显着增加，与未感染的对照小鼠相比，神经元树突标记的丢失、鼠小胶质细胞的激活和人巨噬细胞外植体。HIV p24 也可以在受感染小鼠的大脑中进行量化。这些损伤与 HIV 诱导的脑部炎症和先前小鼠行为异常研究的相关性表明，该模型可用作快速且相关的通量方法来量化 HAND 新疗法的临床前测试。