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.

项目概要 20 世纪 40 年代至 80 年代，美国西南部建立了企业铀矿，导致在周围住宅附近修复不良的场地后面。吸入的、矿场产生的颗粒物已被与血清炎症潜力的增加和随后的血管疾病有关。总理崛起这些铀矿中的特定有毒金属含量往往很高，包括钒、铀，而且通常镍和砷。吸入矿场产生的颗粒物后对全身健康的全面影响是尚不清楚，但这种对神经血管系统的炎症影响可能会促进神经系统疾病和此类机制的阐明尚未明晰。因此，本研究的首要目标建议的目的是更深入地了解矿场产生的 PM- 的机制和因果基础诱发神经血管功能障碍。在初步研究中，我观察到矿场 PM 更为严重与区域背景 PM 相比，对肺部和全身脉管系统具有毒性。此外，类似的研究吸入颗粒物和气体的含量表明血脑屏障功能障碍，可导致神经炎症结果。因此，我的具体目标将服务于三个主要目标：1）进一步探索神经血管反应使用最先进的移动实验室 AirCARE 1 2) 根据矿场得出的 PM 暴露来确定 Rho A/Rho 激酶通路对矿井源性 PM 后神经血管功能障碍的影响暴露；3) 检查这些结果对长期神经病理学和行为的最终影响。这个项目将作为我向独立过渡的五年平台。新墨西哥大学 (UNM) 提供了一个支持性环境，调查人员可以利用多种共享资源。我将充分利用新墨西哥大学健康科学中心的优秀设施，包括生物医学研究和综合神经影像中心 (BRaIN)，该中心设有 MRI、Morris 设有水迷宫和径向臂迷宫。这些研究的数据最终将导致重要的与靠近废弃铀矿的西南部人口有关的信息，以及参与空气质量监管的管理机构。