Multifactorial Assessment of Depleted Uranium Neurotoxicity
Abstract
THIS WAS A 5-YEAR PROJECT TO EXPERIMENTALLY ASSESS THE NEUROTOXICOLOGIC POTENTIAL OF EXPOSURE TO DEPLETED URANIUM (DU), AND THE ROLE OF STRESS IN ALTERING THE TOXICITY. THE PROJECT INVOLVED DETERMINATION OF THE TOXICOKINETICS OF DU IN THE BRAIN, DEVELOPMENT OF A RELEVANT STRESS MODEL, AND STUDY OF NEUROTOXIC EFFFECTS OF A SINGLE (ACUTE) EXPOSURE TO SOLUBLE DU AND TO LONG-TERM EXPOSURE TO IMPLANTED PELLETED DU, AND THEIR MODIFICATION BY STRESS. MAJOR FINDINGS IN THE ACUTE STUDY WERE DOSE-RELATED ELEVATED URANIUM IN BRAIN REGIONS, AND TRANSIENT DECREASE IN DOPAMINE IN THE STRIATUM ON POST-DOSING DAY 3 IN THE HIGH DOSE UNSTRESSED ANIMALS. THERE WERE DU-RELATED DECREASES IN MOTOR ACTIVITY, BODY WEIGHT GAIN AND FORELIMB GRIP STRENGTH. TRANSIENT UREMIA FROM DU DOSE-RELATED RENAL TUBULAR NECROSIS WAS ALSO SEEN, AND MAY HAVE CONTRIBUTED TO THESE CLINICAL FINDINGS. STRESS DID NOT ENHANCE THE DU TOXICITY. MAJOR FINDINGS FROM THE LONG-TERM DU-IMPLANTATION/STRESS STUDY WERE DU DOSE-RELATED INCREASED URANIUM CONCENTRATIONS IN SERUM, KIDNEY AND BRAIN REGIONS IN RATS SACRIFICED 6 MONTHS POST-EXPOSURE, UNAFFECTED BY STRESS. DECREASE IN DOPAMINE IN THE STRIATUM AND EPINEPHRINE IN THE CEREBELLUM WERE SEEN IN THE HIGH DOSE DU GROUP, ALSO UNMODIFIED BY STRESS. THESE STUDIES SHOW THAT URANIUM MOBLIIZED FROM PERIPHERAL SITES CAN ENTER THE BRAIN AND HAVE ADVERSE NEUROLOGIC EFFECTS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2006
- Accession Number
- ADA465204
Entities
People
- Bernard S. Jortner