CORE--NEUROPATHOLOGY

核心--神经病理学

• 批准号: 6205033
• 负责人: EHUD LAVI
• 金额: $ 20.74万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205033
• 关键词: AIDS dementia complex; HIV infections; biomarker; biomedical facility; cell proliferation; chemokine; cytokine receptors; growth factor; human immunodeficiency virus 1; human tissue; immunocytochemistry; in situ hybridization; messenger RNA; neuropathology; nucleic acid sequence; polymerase chain reaction; postmortem; tissue resource /registry; virus antigen; virus cytopathogenic effect

The central hypothesis of this program project application is that the pathogenesis of HIV encephalopathy may involve either direct mechanisms in which highly restricted HIV infections of glia or neurons lead to neuronal dysfunction, or indirect mechanisms in which infected microglial cells, produce viral proteins, cytokines or chemokines which in turn act on glia or neurons leading to dysfunction. The Neuropathology Core will continue to explore these hypotheses by studies of the brains of patients dying with HIV infection. These brains will be used for two purposes, (i) as a tissue bank to support studies under other projects in this program, and (ii) histologically based studies to compare the cellular distribution of HIV, cytokines, chemokine and their receptors and growth factors (e.g. PDGF), to pathological lesions and proliferation markers of astrocytes (GFAP) microglia and endothelial cells (RCA-1). (I) Tissue bank. About 5-10 brains will be collected each year under the aegis of the autopsy service at the Hospital of the University of Pennsylvania. These brains, in addition to the existing collection of 25 brains will constitute a tissue bank, with tissues stored in various ways to optimize them as a resource for other projects under this program, including PCR amplification of gene sequences, and histological section based studies of viral chemokine receptors mRNA, and standard neuropathological stains. (ii) Neuropathological mapping. Selected brains will be used to map the distribution of neuropathological lesions, distribution of HIV genome by in situ PCR, HIV antigen by immunohistochemistry, and mRNA by in situ hybridization for selected chemokines, chemokine receptors, growth factors (PDGF), and markers of cell proliferation such as GFAP and RCA-1. (iii) Assistance with the design and interpretation of morphological and neuropathological studies of other projects including the analysis of cell cultures and mouse brains.

该计划项目申请的中心假设是，HIV 脑病的发病机制可能涉及直接机制，即高度限制的 HIV 感染神经胶质细胞或神经元导致神经元功能障碍，或间接机制，即受感染的小胶质细胞产生病毒蛋白、细胞因子或病毒蛋白。趋化因子反过来作用于神经胶质或神经元，导致功能障碍。神经病理学核心将继续通过研究死于艾滋病毒感染的患者的大脑来探索这些假设。这些大脑将用于两个目的，（i）作为组织库来支持该计划其他项目下的研究，以及（ii）基于组织学的研究，以比较艾滋病毒、细胞因子、趋化因子及其受体和生长因子的细胞分布（例如 PDGF）、星形胶质细胞（GFAP）、小胶质细胞和内皮细胞（RCA-1）的病理病变和增殖标志物。 （一）组织库。宾夕法尼亚大学医院尸检服务机构每年都会收集大约 5-10 个大脑。除了现有的 25 个大脑之外，这些大脑将构成一个组织库，其中以各种方式存储组织，以优化它们作为该计划下其他项目的资源，包括基因序列的 PCR 扩增以及基于组织学切片的研究病毒趋化因子受体 mRNA 和标准神经病理学染色。 (ii) 神经病理学绘图。选定的大脑将用于绘制神经病理病变的分布图，通过原位 PCR 绘制 HIV 基因组分布图，通过免疫组织化学绘制 HIV 抗原图，通过原位杂交绘制所选趋化因子、趋化因子受体、生长因子 (PDGF) 和细胞标记物的 mRNA 分布图增殖如 GFAP 和 RCA-1。 (iii) 协助设计和解释其他项目的形态学和神经病理学研究，包括细胞培养物和小鼠大脑的分析。