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.
Poor remediation of abandoned commercial uranium mines throughout the Southwestern United States has subjected Native tribal communities to metal-based (uranium, vanadium, arsenic) environmental exposures. Recent data suggest that inhalation of fugitive mine-site derived dust may have neurovascular consequences. The proposed research intends explore this relationship and evaluate the mechanism underlying mine-site derived PM-induced endothelial dysfunction and long-term neurological consequences.
|Assad, Nour; Sood, Akshay; Campen, Matthew J et al. (2018) Metal-Induced Pulmonary Fibrosis. Curr Environ Health Rep 5:486-498|