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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：
10392427
负责人：
Katherine Zychowski
金额：
$ 24.62万
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 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10392427
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.

项目总结