Brain Accumulation of Depleted Uranium in Rats Following 3- or 6-Month Treatment With Implanted Depleted Uranium Pellets By: Vanessa A. Fitsanakis, Keith M. Erikson , Stephanie J. Garcia, Lars Evje, Tore Syversen, and Michael Aschner Fitsanakis, V.A., Erikson, K.M., Garcia, S.J., Evje, L., Syversen, T., Aschner, M. (2006) Brain Accumulation of depleted uranium in rats following 3 or 6 month treatment with implanted depleted uranium pellets. Biol Trace Elem Res 111: 185-197. Made available courtesy of: Springer-Verlag *** Note: Figures may be missing from this format of the document *** Note: The original publication is available at http://www.springerlink.com/ Abstract: Depleted uranium (DU) is used to reinforce armor shielding and increase penetrability of military munitions. Although the data are conflicting, DU has been invoked as a potential etiological factor in Gulf War syndrome. We examined regional brain DU accumulation following surgical implantation of metal pellets in male Sprague–Dawley rats for 3 or 6 mo. Prior to surgery, rats were randomly divided into five groups: Nonsurgical control (NS Control); 0 DU pellets/20 tantalum (Ta) pellets (Sham); 4 DU pellets/16 Ta pellets (Low); 10 DU pellets/10 Ta pellets (Medium); 20 DU pellets/0 Ta pellets (High). Rats were weighed weekly as a measure of general health, with no statistically significant differences observed among groups in either cohort. At the conclusion of the respective studies, animals were perfused with phosphate-buffered saline, pH 7.4, to prevent contamination of brain tissue with DU from blood. Brains were removed and dissected into six regions: cerebellum, brainstem (pons and medulla), midbrain, hippocampus, striatum, and cortex. The uranium content was measured in digested samples as its 238 U isotope by high-resolution inductively coupled plasma– mass spectrometry. After 3 mo postimplantation, DU significantly accumulated in all brain regions except the hippocampus in animals receiving the highest dose of DU (p < 0.05). By 6 mo, however, significant accumulation was measured only in the cortex, midbrain, and cerebellum (p < 0.01). Our data suggest that DU implanted in peripheral tissues can preferentially accumulate in specific brain regions. Index Entries: Depleted uranium; heavy metal toxicity; Gulf War syndrome; blood–brain barrier transport; ICP-MS. Article: INTRODUCTION Naturally occurring uranium (U) consists of three isotopes: 234 U (0.0055%), 235 U (0.720%), and 238 U (99.27%). During the production of U for nuclear fuel and weapons, the highly radioactive isotope, 234 U, is enriched, leaving the remaining U relatively depleted of both the 234 U and 235 U isotopes. This resulting mixture of U, known as ―depleted uranium‖ (DU), is mainly the 238 U isotope (99.8%, with 0.001% 234 U and 0.20% 235 U), which is 40% less radioactive than natural U and is 1.7 times more dense than lead (Pb). Because of its unique physiochemical properties, DU has many civilian and military uses. For example, it is utilized in medical equipment radiation shields, aircraft counterbalances, and, until the 1980s, as a component in dental porcelains (1). Potential health problems related to DU exposure were highlighted following the first Gulf War (1991) because of its use in reinforcing armor plating of military vehicles and as a component in armor-piercing munitions. Following service in the Gulf War, many veterans reported various health problems, including headaches, dizziness, fatigue, bone and joint pain, muscle weakness, memory loss, problems with sleep and concentration, skin rashes and sores, and various gastrointestinal problems (2–4). Together these symptoms are known as Gulf War syndrome (GWS). Additional concern regarding health problems resulted following the war operations in Serbia, as well as the current use of DU in munitions and shielding in Iraq.