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Multifactorial Assessment of Depleted Uranium Neurotoxicity

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Annual rept. 1 Oct 2001-30 Sep 2002

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This is a three-year study on the neurotoxic potential of depleted uranium DU in laboratory rats. The effect of stress on DU kinetics and toxicity will also be evaluated. Previous studies with Gulf War veterans and experimental animals exposed to embedded DU suggest that neurotoxicity may result from DU exposure McDiarmid et al. 2000 Pellmar et al.1 1999. The current investigation is designed to assess the neurotoxic potential of acute and chronic exposure to DU and the contribution of stress to expression of DU neurotoxicity. All studies are being performed with adult male Sprague-Dawley rats. Acute exposures are being performed with uranyl acetate, while chronic exposures will utilize solid DU particles. The kinetics of DU in various brain regions is being determined by inductively coupled plasma-mass spectrometry lCP-MS analysis in cortex, hippocampus, striatum, and cerebellum between 8 hours and 30 days after a single DU administration. Neurotoxicity will be assessed with behavioral, morphological, and biochemical endpoints. Behavioral assessment of neurotoxicity will utilize Functional Observation Battery FOB, motor activity, and tests of learning and memory by passive avoidance. Biochemical analyses will include quantification of neurotransmitters, determination of receptor number, indicators of oxidative stress, and changes in gene expression. Biochemical determinations will be made in the same brain regions examined for DU kinetics. Morphological studies will employ perfusion-fixation, multilevel sampling of the nervous system and contemporary light microscopic procedures to allow detailed evaluation of any lesions. Stress will be applied to animals using forced swimming as described in previous Gulf War Illness studies. These studies will help define the neurotoxic potential of DU and by correlation with serum uranium, aid in identifying individuals at risk for DU neurotoxicity.

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  • Medicine and Medical Research

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