Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium
Abstract
The chemical properties and high density of depleted uranium (DU) render the metal well suited for military purposes, but knowledge of DU neurotoxicity and its treatment is lacking. This project is designed to test the hypothesis that long-term administration of a free radical trapping agent and/or an NMDA receptor antagonist will reduce neurotoxicity resulting from chronic exposure to DU. This hypothesis is consistent with previous observations ensuing from chronic intramuscular DU pellet implants in rats, and is based on the anticipation that specific pharmacological agents will reverse signs of DU-induced oxidative stress. As prescribed by the Statement of Work, efforts were initiated in year 1 on Tasks 1 (drug therapies to reverse DU-induced elevations in extracellular glutamate) and 2 (brain DU concentrations) utilizing experimental groups (C, 300, and 600 mg DU) exposed for 9 months. Task 1 incorporates chronic neuroprotectant drug administration via implanted osmotic minipumps to address these objectives. Progress has been achieved on each Task, and remaining subject cohorts will be analyzed in year 2. Efforts have also begun to set up the biochemical assays to achieve Task 3 (biochemical markers of DU-induced oxidative stress in hippocampal tissue). Thus, progress is proceeding according to the schedule specified in the Statement of Work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2008
- Accession Number
- ADA494588
Entities
People
- Stephen M. Lasley
Organizations
- University of Illinois at Chicago