Blood-Brain Barrier Transport of Uranium
Abstract
Recent studies of Gulf War veterans with depleted uranium (DU) embedded fragments in their soft tissues point to DU-induced effects on neurobehavioral and cognitive function. These observations are corroborated by electrophysiological changes in hippocampal slices isolated from rats embedded with DU fragments. Notably, studies from the same group also suggest, for the first time, that uranium accumulates within brain tissue. It is presently unknown how uranium is transported into the brain, and there are no pharmacological modalities to reduce its accumulation within the central nervous system (CNS) . The purpose of this project is to identify the substrate specificity of uranium transport in the CNS, the working hypothesis being that the divalent metal transporter (DMT-1) which has an unusually broad substrate range that includes Fe(2+), Zn(2+), Mn(2+), Co(2+), Cd(2+), Cu(2+), Ni(2+), and Pb(2+), is mediating uranium transport in the CNS. This project focuses on examining this hypothesis from an in vitro approach utilizing endothelial cell culture models as well as an in vivo approach to delineate the pharmacokinetics of uranium transport across the blood brain barrier (BBB) in rats embedded with DU fragments. The studies will test the hypothesis that a relationship exists between blood and brain uranium concentrations, determining whether rats with the highest blood uranium concentrations also accumulate the highest uranium concentrations in the CNS. Thus, the studies will facilitate risk assessment in veterans, and will determine whether those with the highest uranium blood levels are more prone to accumulate uranium in the CNS compared to veterans with low blood uranium levels.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA446997
Entities
People
- Michael Aschner
Organizations
- Vanderbilt University Medical Center