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; 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.

该计划项目应用的中心假设是，HIV脑病的发病机制可能涉及直接机制，其中高度限制的神经胶质或神经元的HIV感染导致神经元功能障碍或间接机制，或者在该机制中产生病毒蛋白，cytokines或Chemia in Neuron in tern in tern in tern in Act oct oct oct oct oct oct oct oct oct oct oct oct oct oct octia s of Act oct oct oct。神经病理学核心将通过研究死于HIV感染的患者的大脑的研究，继续探索这些假设。 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）组织库。每年在宾夕法尼亚大学医院的尸检服务的宙斯盾下，每年将收集约5-10个大脑。除现有25个大脑的现有收集外，这些大脑还将构成组织库，其组织以各种方式存储，以优化它们作为该程序下其他项目的资源，包括基因序列的PCR扩增以及基于组织学的基于病毒趋化因子受体mRNA的研究，以及标准神经病理学染色。 （ii）神经病理图。选定的大脑将用于绘制神经病理病变的分布，原位PCR对HIV基因组的分布，免疫组织化学的HIV抗原和通过原位杂交的MRNA，用于选定趋化因子，趋化因子受体，生长因子（PDGF）以及诸如GFAP和RCA-1的细胞扩散的标记。 （iii）协助对其他项目的形态和神经病理学研究的设计和解释，包括分析细胞培养物和小鼠大脑。