CORE--NEUROPATHOLOGY

核心--神经病理学

• 批准号: 6596372
• 负责人: HARRY V. VINTERS
• 金额: $ 26.84万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6596372
• 关键词: Alzheimer's disease; Lewy body; biomedical facility; brain disorder diagnosis; cerebral ischemia /hypoxia; cerebrovascular disorders; histopathology; human tissue; infarct; neural degeneration; neuropathology; postmortem

The goals of the Neuropathology Core (NPC) will be to provide standardize neuropathologic assessment of brains obtained at autopsy from study patients who have been followed clinically, using neuropsychological evaluations and neuroimaging, in order to characterize the relative contributions of ischemic vascular lesions and parenchymal degenerative changes (e.g. of Alzheimer disease) to a given patient's dementia. Comparisons of specific neuropathologic parameters (see below) will be made among ischemic vascular dementia (IVD), Alzheimer and control patients. We will operationalize assessment of neuropathologic substrates of IVD by evaluating both (a) extent, and (b) distribution of encephalomalacic lesions that may contribute to dementia. A neuropathologic data base will be maintained and data will be provided to other projects as necessary to facilitate correlations between pre- mortem (including metabolic) imaging studies and postmortem brain findings, with an emphasis on defining radiographic features on lacunar infarcts, and their possible impact upon cortical integrity by mechanisms of retrograde and trans-synaptic degeneration. Possible neuroanatomical correlates of ischemic vascular dementia )IVD) to be evaluated in detail will include changes within white matter (axons, myelin sheaths) and densities and sizes of neurons projecting into the white matter (in conjugation with Project #3). Possible neuropathologic substrates of IVD to be evaluated, using immunohistochemistry and quantitative morphometry, will include (a) microvascular lesions characterized as abnormal distributions/densities of glucose transporter-immunoreactive capillaries, and hypertrophic arterioles, (b) secondary injurious effects of microvasculopathy upon adjacent brain parenchyma (e.g. axon/myeline densities of glucose transporter-immunoreactive capillaries, and hypertrophic arterioles, (b) secondary injurious effects of microvasculopathy upon adjacent brain parenchyma (e.g. axon/myelin densities , APP expression) and inflammatory/reactive cells (microglia, astrocytes), and (c) hippocampal abnormalities indicative of hippocampal sclerosis or scarring. Neuropathologic data will be provided to the investigational projects and all clinical/experimental data will be re- evaluated in these projects in light of neuropathologic outcomes. The intended result is to provide the most detailed available pathophysiologic representation of IVD based upon multi-modality functional and neuroanatomical patient evaluation.

神经病理学核心（NPC）的目标将是对使用神经心理学评估和神经影像受到临床遵循的研究患者获得的大脑进行标准化的神经病理学评估，以表征缺血性血管性病变和良好疾病的相对贡献。特定神经病理学参数的比较（见下文）将在缺血性血管痴呆（IVD），阿尔茨海默氏症和对照患者之间进行。我们将通过评估（a）范围和（b）可能导致痴呆症的脑呈脑乳清病变的分布来对IVD的神经病理底物进行评估。将维护神经病理数据库，并根据需要向其他项目提供数据，以促进验尸（包括代谢）成像研究与事后大脑发现之间的相关性，并重点是将放射线学特征定义在骨质梗塞上，以及它们通过逆行机制对皮质完整性的影响。要详细评估的缺血性血管性痴呆）IVD的神经解剖学相关性将包括白质（轴突，髓鞘）内的变化，以及投射到白质（与项目＃3结合结合）的神经元的密度和大小。使用免疫组织化学和定量形态计量学评估IVD的神经病理学底物将包括（a）（a）葡萄糖转运蛋白转运蛋白 - 免疫反应性反应性毛细血管的异常分布/密度的微血管病变（a），脑部和过度脑静脉曲张，（B）偶然性效应，（B）偶然的脑膜炎。 （例如，葡萄糖转运蛋白免疫反应性毛细血管和肥大动脉的轴突/肌线密度，（（b）微血管病患者对邻近脑实质的继发性伤害作用指示海马硬化或疤痕的异常。