LOCALIZATION AND CHARACTERIZATION OF IRON DEPOSITS IN MULTIPLE SCLEROSIS

多发性硬化症中铁沉积物的定位和表征

• 批准号: 8362394
• 负责人: HELEN NICHOL
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362394
• 关键词: Affect; Animal Model; Autacoids; Autopsy; Blood capillaries; Brain; Brain Drains; Calcium; Cerebrum; Chemicals; Chemistry; Chronic; Copper; Data; Demyelinations; Deposition; Diagnosis; Disease; Elements; Face; Fluorescence; Freezing; Funding; Grant; Healed; Human; Image; Iron; Link; Lipopolysaccharides; Magnetic Resonance Imaging; Maps; Metals; Microglia; Modeling; Multiple Sclerosis; Multiple Sclerosis Lesions; Mus; National Center for Research Resources; Optics; Patients; Principal Investigator; Process; Radiation; Rattus; Relapsing-Remitting Multiple Sclerosis; Research; Research Infrastructure; Resolution; Resources; Role; Scanning; Slice; Source; Synchrotrons; Thick; Time; Tissues; United States National Institutes of Health; Venous Insufficiency; Virus Diseases; Work; Zinc; brain tissue; capillary; cost; healing; immunopathology; interest; mouse model; sciatic nerve; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In this proposal we combine the unique capabilities of synchrotron x-ray fluorescence (XRF) and magnetic resonance imaging (MRI) with classical immunopathology to elucidate the role of iron deposits in human multiple sclerosis (MS) and in animal models that recapitulate important features of human MS. First, thick human autopsy brain slices, both MS affected and unaffected, will be imaged using MRI sequences commonly used in the diagnosis of MS patients. Using the MRI image as a guide, each brain will be sliced 2 mm thick and the fresh face will be mapped for iron and other abundant elements (calcium, copper and zinc) using rapid-scanning XRF (100 micron beam). The ability to map multiple elements, by SRS-XRF, is crucial because preliminary data shows that MS lesions are low in zinc, regions of active disease are high in iron and copper is also abnormal. Regions of interest will be excised for microprobe analysis and immunopathology and to determine the chemical form of iron. Iron chemistry associated with active disease (microglia) will be compared with iron seen around vessels draining the brain that may result from chronic cerebral venous insufficiency (CCSVI). CCSVI is linked to many types of MS. Where tissue is available, iron K-edge spectra will be collected at 10K from ROI excised from frozen human brain tissue. In a second study combining MRI with rapid scanning (50 micron beam) and microprobe XRF, we will map iron in a mouse model of progressive MS. In this murine model, demyelination is produced by viral infection. In a third study we will examine the role of multiple metals in the healing process using a rat model of focal demyelination in the brain and sciatic nerve induced by lipopolysaccharide. This is a model of relapsing remitting MS in which the healing process and remyelination can be followed over time. Preliminary work shows that a 20 micron capillary optic will provide the sufficient flux and resolution for initial mapping in this study.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在此提案中，我们将同步加速器X射线荧光（XRF）和磁共振成像（MRI）的独特能力与经典免疫病理学结合在一起，以阐明铁沉积在人类多发性硬化症（MS）中的作用以及在重新培养人类MS重要特征的动物模型中。 首先，将使用通常用于MS患者诊断的MRI序列对厚的人类尸检脑切片进行成像。使用MRI图像作为指导，将使用快速扫描的XRF（100微米束）将每个大脑切成2 mm厚的厚度为2 mm，并将新鲜面映射为铁和其他丰富的元素（钙，铜和锌）。通过SRS-XRF绘制多个元素的能力至关重要，因为初步数据表明，锌的MS病变较低，活性疾病区域的铁和铜也异常。感兴趣的区域将被切除以进行微探针分析和免疫病理学，并确定铁的化学形式。将与活性疾病（小胶质细胞）相关的铁化学与在慢性脑静脉功能不全（CCSVI）可能导致的大脑周围看到的铁进行比较。 CCSVI链接到许多类型的MS。在可用组织的地方，将从冷冻的人脑组织中切除的ROI处收集铁K边缘光谱。在第二项研究中，将MRI与快速扫描（50微米束）和微探针XRF结合在一起，我们将在渐进式MS的小鼠模型中绘制铁。 在这种鼠模型中，脱髓鞘是由病毒感染产生的。 在第三项研究中，我们将使用脂多糖诱导的大脑和坐骨神经中的局灶性脱髓鞘模型来检查多种金属在愈合过程中的作用。这是一种复发汇出MS的模型，其中可以随着时间的推移遵循愈合过程和透明度。初步工作表明，在本研究中，20微米毛细管光学元件将提供足够的通量和分辨率。