Neurological effects of acute uranium exposure with and without stress.

Circulating uranium rapidly enters the brain and may cause adverse effects on the nervous system that are potentially modulated by stress. In this study, the neurological effects of a single intramuscular injection of 0, 0.1, 0.3, or 1 mg uranium/kg (as uranyl acetate, UA) in rats were examined in the presence and absence of stress. Treatment with UA produced time and dose-dependent increases in serum and regional brain uranium levels. While serum levels returned to control levels by day 30, brain levels remained elevated. Application of stress did not affect the distribution or retention of uranium. Exposure to 1 mg U/kg significantly decreased ambulatory activity, weight gain, forelimb grip strength and transiently impaired working memory. Effects on grip strength and memory were prevented by application of stress prior to uranium exposure. Striatal dopamine content was reduced by 30% 3 days after treatment with 1mg/kg (59+/-6 nmol/mg tissue versus 41+/-5 nmol/mg tissue), but levels returned to control 7 days after uranium exposure. The effect on dopamine was ameliorated by prior application of stress. Exposure to UA did not alter 3,4 dihydroxyphenylacetic acid (DOPAC) levels or numbers of D2 receptors in the striatum. No effect of uranium or stress was observed on levels of GABA, serotonin, norepinephrine, or glutathione (GSH) in the striatum, hippocampus, cerebellum, or cortex. These results indicate that single intramuscular exposures to uranium produce sustained elevation of brain uranium levels and at doses above 0.3 mg/kg can have adverse neurological effects. Application of stress prior to uranium administration modulates neurological effects, but the mechanism is not due to effects on uranium distribution. Uranium exposure also produced renal toxicity which must be considered to accurately assess the effects of uranium on neurological function.

Morphological measurement of neurotoxic injury in the peripheral nervous system: preparation of material for light and transmission electron microscopic evaluation.

An important method of assessing experimental neurotoxic injury is the pathologic examination of the nervous system. Methods for fixation, sampling, and preparation of peripheral nervous system tissues for critical pathological neurotoxicology studies are presented. Fixation of tissue is carried out using either perfusion-fixation of laboratory animals or immersion-fixation of dissected nerve segments. Dissection of the peripheral nervous system (from perfusion-fixed animals) is done to allow for multilevel sampling. Focus is on use of epoxy resin embedding tissue sections for optimal light microscopic resolution. Protocols for processing, sectioning, and staining for light and transmission electron microscopy are provided. A protocol for teasing and microscopic study of individual myelinated fibers is provided.