Neurovascular Consequences of Inhaled Uranium Mine-Site Dust Exposure

吸入铀矿场粉尘暴露对神经血管的影响

基本信息

批准号：
10164782
负责人：
Katherine Zychowski
金额：
$ 24.73万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-15 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10164782
关键词：
Acute Advisory Committees Airborne Particulate Matter Arizona Arsenic Arterial Fatty Streak Automobile Driving Behavior Behavioral Biomedical Research Blood - brain barrier anatomy Blood Circulation Blood Vessels Cardiovascular Diseases Carotid Arteries Carotid Artery Plaques Communication Research Communities Data Development Dust Endothelial Cells Endothelium Environmental Exposure Environmental Health Environmental Pollution Exposure to Extravasation Functional disorder Future Gases Generations Goals Health Health Sciences Heavy Metals Home Impairment In Vitro Incidence Inflammation Inflammatory Inflammatory Response Ingestion Inhalation Inhalation Exposure Intervention Laboratories Lead Link Lung Magnetic Resonance Imaging Mentorship Metals Mining Navajo Neurologic New Mexico Nickel Outcome Particulate Particulate Matter Pathologic Pathology Pathway interactions Pharmacy (field)Plants Population Radial Recording of previous events Research Research Infrastructure Research Personnel Research Proposals Resource Sharing Rho-associated kinase Role Series Serum Site Southwestern United States Stroke Techniques Thrombus Tissues Transient Ischemic Attack Transition Elements Universities Uranium Vanadium Vascular Diseases Work air quality regulation arm base brain parenchyma burden of illness career cerebrovascular drinking water endothelial dysfunction exposure route in vivo morris water maze mouse model nervous system disorder neuroimaging neuroinflammation neuropathology neurovascular neurovascular unit particle plaque lesion prevent remediation response rho supportive environment toxic metal tribal community wasting

项目摘要

PROJECT SUMMARY Corporate uranium mines were established in the Southwestern United States from the 1940s-1980s, leaving behind poorly remediated sites near surrounding residential homes. Inhaled, mine-site derived PM has been associated with an increase in serum inflammatory potential and subsequent vascular disease. The PM arising from these uranium mines tends to be high in specific toxic metals including vanadium, uranium, and often nickel and arsenic. The full scope of systemic health effects following inhaled mine-site derived PM is unknown, but such inflammatory impacts to the neurovasculature could promote neurological diseases and the elucidation of such mechanisms has yet to be discerned. Therefore, the primary objective of this research proposal is to develop a deeper understanding of the mechanistic, causal basis for mine-site derived PM- induced neurovascular dysfunction. In preliminary studies, I have observed that mine site PM is more acutely toxic to the lungs and systemic vasculature compared to regional background PM. Furthermore, similar studies of inhaled particulates and gases demonstrate a BBB dysfunction that can drive neuroinflammatory outcomes. Therefore, my specific aims will serve three primary objectives: 1) to further explore neurovascular responses following mine-site derived PM exposure using state-of-the art mobile laboratory AirCARE 1 2) to determine the contribution of the Rho A/Rho kinase pathway on neurovascular dysfunction following mine-site derived PM exposure and 3) to examine the ultimate impact of these outcomes on long-term neuropathology and behavior. This project will serve as a five-year platform for my transition to independence. The University of New Mexico (UNM) offers a supportive environment where investigators can take advantage of several shared resources. I will take full advantage of the outstanding facilities at the University of New Mexico Health Sciences Center, including the Biomedical Research and Integrative Neuroimaging Center (BRaIN), where the MRI, Morris Water Maze and Radial Arm Maze are housed. Data from these studies will ultimately lead to essential information pertinent to Southwestern populations in close proximity to abandoned uranium mines, as well as governing agencies involved in air-quality regulations.

项目摘要从1940年代1980年代开始，在美国西南部建立了铀矿业在住宅周围房屋附近的补救局局部遗址不佳的后面。吸入的，矿场派生的PM已与血清炎症潜力增加和随后的血管疾病有关。下午出现这些铀矿中的特定有毒金属往往很高，包括钒，铀和通常镍和砷。吸入矿场派生的PM后，全身健康效应的全部范围为未知，但这种炎症对神经血管系统的影响可能会促进神经系统疾病和阐明这种机制尚未辨别。因此，这项研究的主要目标建议是对矿物位点派生的PM-的机械性，因果关系的更深入了解 - 诱导神经血管功能障碍。在初步研究中，我观察到矿场站点PM更敏锐与区域背景PM相比，对肺部和全身脉管系统有毒。此外，类似的研究吸入的颗粒物和气体表现出BBB功能障碍，可驱动神经炎症结果。因此，我的具体目标将达到三个主要目标：1）进一步探索神经血管反应使用最先进的移动实验室空气护理1 2）确定矿场点派生的PM暴露。 RHO A/RHO激酶途径在矿场衍生的PM之后对神经血管功能障碍的贡献暴露和3）检查这些结果对长期神经病理学和行为的最终影响。该项目将成为我过渡到独立性的五年平台。新墨西哥大学（UNM）提供了一个支持性环境，调查人员可以利用几个共享资源。我将充分利用新墨西哥大学健康科学中心的出色设施包括生物医学研究和综合神经影像中心（大脑），MRI，莫里斯水迷宫和径向手臂迷宫被安置。这些研究的数据最终将导致必不可少的与西南人口相关的信息与废弃的铀矿非常接近涉及空气质量法规的管理机构。