{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:53:18Z","timestamp":1791399198876,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,5,27]],"date-time":"2012-05-27T00:00:00Z","timestamp":1338076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Contrast Media &amp; Molecular"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p>Manganese is a vital element and cofactor of many key enzymes, but it is toxic at high levels, causing pronounced disturbances in the mammalian brain. Magnetic resonance imaging (MRI) studies using manganese ions as a paramagnetic contrast agent are often limited by the neurotoxicity of Mn<jats:sup>2+<\/jats:sup>. In this work, we have explored a new <jats:italic>in vivo<\/jats:italic> model to study Mn<jats:sup>2+<\/jats:sup> uptake, distribution and neurotoxicity in mice by subcutaneous implantation of mini\u2010osmotic pumps delivering MnCl<jats:sub>2<\/jats:sub> continuously for 21\u2009days. Fractionated injections can reduce the toxicity; however, constant administration at very low doses using osmotic pumps caused a substantial effect on the <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> contrast in MRI while reducing toxicity. Manganese\u2010enhanced MRI documented fast but reversible Mn<jats:sup>2+<\/jats:sup> 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<jats:sup>2+<\/jats:sup> accumulated as early as the first days after implantation, with a fast dispersal 9\u2009days after stopping a 12\u2010days Mn<jats:sup>2+<\/jats:sup> exposure. Prominent Mn<jats:sup>2+<\/jats:sup> accumulation was also seen in salivary glands and in the endocrine thyroid and posterior pituitary gland. These structures with enhanced Mn<jats:sup>2+<\/jats:sup> accumulation correlated well with those showing high expression of the secretory pathway Ca<jats:sup>2+<\/jats:sup>\/Mn<jats:sup>2+<\/jats:sup>\u2010ATPase (SPCA1), i.e. a transporter that could take part in Mn<jats:sup>2+<\/jats:sup> detoxification. Our new experimental model for continuous low\u2010dosage administration of Mn<jats:sup>2+<\/jats:sup> is an easy alternative for enhancing Mn<jats:sup>2+<\/jats:sup>\u2010based contrast in MEMRI studies, and might provide insight into the etiology of neuropathologies resulting from chronic Mn<jats:sup>2+<\/jats:sup> exposure <jats:italic>in vivo<\/jats:italic>. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cmmi.1469","type":"journal-article","created":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T09:57:57Z","timestamp":1338458277000},"page":"426-434","source":"Crossref","is-referenced-by-count":48,"title":["Evaluation of manganese uptake and toxicity in mouse brain during continuous MnCl<sub>2<\/sub> administration using osmotic pumps"],"prefix":"10.1002","volume":"7","author":[{"given":"M. R.","family":"Sep\u00falveda","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Transport Systems Department of. 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