Differential deposition of manganese in the rat brain following subchronic exposure to manganese: a T(1)-weighted MRI study

BACKGROUND: Manganism is a central nervous system (CNS) disorder caused by toxic exposure to manganese (Mn). Manganism has been related to occupational exposures, liver diseases, prolonged parenteral nutrition and abuse of illicit drugs. Initially manifested by a reversible neuropsychiatric syndrome (locura manganica), the main symptoms and signs of manganism are emotional lability, compulsive behavior and visual hallucinations. Locura manganica is followed by an irreversible extrapyramidal syndrome, the onset of which occurs years after chronic exposure. OBJECTIVES: To characterize the regional distribution of Mn in the rat brain after subchronic exposure to Mn. This animal model holds special clinical relevance, reflecting the earlier clinical stages of manganism, before chronic exposure to Mn exerts its irreversible effects. METHODS: Sprague-Dawley rats were intravenously injected with MnCl(2) weekly, for a total of 14 weeks – approx. 1/10 of the lifetime of the rat. T(1)-weighted MRI was employed as a sensitive tool for detecting the distribution of Mn deposition in brain tissues, as evidenced by areas of T(1)-weighted hyperintense signals. RESULTS: A consistent region-specific pattern of T1-weighted hyperintensities was observed in the brains of Mn treated rats. Cortical hyperintensities were prominent in the hippocampus and dentate gyrus. Hyperintensities were also observed in the olfactory bulbs, pituitary gland, optic nerves and chiasma, pons, midbrain tegmentum, habenula, lentiform and caudate nuclei, thalamus, chorioid plexus and cerebellar hemispheres. CONCLUSIONS: Prominent Mn depositions, evidenced by T(1)-weighted hyperintensities in the hippocampus after subacute exposure to Mn, are compatible with the clinical picture of manganism during its early stages; and may explain its pathophysiology.