Inhalation of Uranium Oxide Aerosois: CNS Deposition, Neurotoxicity, and Role in Gulf War Illness

Abstract

This study investigates the potential for inhaled uranium oxide (UO) aerosols to penetrate the nose-brain barrier, directly enter the central nervous system (CNS), distribute within the CNS, and result in slowly developing neurotoxicity. Inhalation exposures to depleted uranium (DU) may have occurred during the GW in several scenarios of varying duration and airborne uranium concentration. Nasal inflammation could alter sensitivity to uranium uptake. Nephrotoxic and pulmonary effects are evaluated to determine whether CNS effects can occur at lower thresholds than nephrotoxic effects. In year 4, we focused on analysis of tissues following long-term (30 days), moderate dose (1 mg/m3) uranium inhalation, with or without induced nasal inflammation. Brain uptake was only seen in a subset of rats (2 of 12) and only in the olfactory bulb. Similarly, rats re-exposed to long-term, low dose uranium in combination with induced nasal damage also showed a limited uranium uptake (3 of 24 rats). Histological evaluation of olfactory bulbs revealed an increased astrogliosis and an upregulation of tyrosine hydroxylase (a marker for dopaminergic neurons) 180 days after uranium inhalation. No loss of large spinal motor neurons was seen at the same timepoint. Uranium-associated kidney pathology was not notable at this exposure regimen, but alveolar macrophage hyperplasia and particle inclusion were uniform and persistent, apparent even at 180 days post 30 day exposure.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA454899

Entities

People

  • Fletcher F. Hahn
  • Graham Bench
  • Johnnye L. Lewis

Organizations

  • University of New Mexico

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Anesthesia
  • Brain
  • Cells
  • Central Nervous System
  • Ceramic Materials
  • Chemical Synthesis
  • Chemistry
  • Health Services
  • Inflammation
  • Macrophages
  • Medical Personnel
  • Motor Neurons
  • Nervous System
  • Neurons
  • Nose
  • Particles
  • Spinal Cord

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Immunology
  • Nuclear Non-Proliferation and International Security