Blood-Brain Barrier Transport of Uranium
Annual rept. 1 Sep 2004-31 Aug 2005
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
Pagination or Media Count:
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 Fe2, Zn2, Mn2, Co2, Cd2, Cu2, Ni2, and Pb2, 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.
- Medicine and Medical Research
- Weapons Effects (Biological)