Ciencias

Contrast Media Mol Imaging. 2012 Jul-Aug;7(4):426-34. doi: 10.1002/cmmi.1469.
Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl2 administration using osmotic pumps.Sepúlveda MR, Dresselaers T, Vangheluwe P, Everaerts W, Himmelreich U, Mata AM, Wuytack F.
Source
Laboratory of Cellular Transport Systems, Department of Molecular Cell Biology, Faculty of Medicine,Katholieke Universiteit Leuven, Belgium.
Abstract
Manganese is a vital element and cofactor of many key enzymes, but it is toxic at high levels, causing pronounced disturbances in themammalianbrain. Magnetic resonance imaging (MRI) studies using manganese ions as a paramagnetic contrast agent are often limited by the neurotoxicity of Mn(2+) . In this work, we have explored a new in vivo modelto study Mn(2+) uptake, distribution and neurotoxicity in mice by subcutaneous implantation of mini-osmotic pumps delivering MnCl(2) continuously for 21 days. Fractionated injections can reduce thetoxicity; however, constant administration at very low doses using osmotic pumps caused a substantial effect on the T(1) contrast in MRI while reducing toxicity. Manganese-enhanced MRI documented fastbut reversible Mn(2+) deposition largely in glomerular and mitral cell layers of the olfactory bulb, in the CA3 area of the hippocampus, and in the gray matter of the cerebellum. Mn(2+) accumulated asearly as the first days after implantation, with a fast dispersal 9 days after stopping a 12-days Mn(2+) exposure. Prominent Mn(2+) accumulation was also seen in salivary glands and in the endocrinethyroid and posterior pituitary gland. These structures with enhanced Mn(2+) accumulation correlated well with those showing high expression of the secretory pathway Ca(2+) /Mn(2+) -ATPase (SPCA1),i.e. a transporter that could take part in Mn(2+) detoxification. Our new experimental model for continuous low-dosage administration of Mn(2+) is an easy alternative for enhancing Mn(2+) -based...