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Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Vousden, DA; Cox, E; Allemang-Grand, R; Laliberte, C; Qiu, LR; Lindenmaier, Z; Nieman, BJ; (2018) Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration. NeuroImage , 173 pp. 411-420. 10.1016/j.neuroimage.2018.02.046. Green open access

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Abstract

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique in rodent neuroimaging studies. Traditionally, Mn2+ is delivered to animals via a systemic injection; however, this can lead to toxic effects at high doses. Recent studies have shown that subcutaneously implanted mini-osmotic pumps can be used to continuously deliver manganese chloride (MnCl2), and that they produce satisfactory contrast while circumventing many of the toxic side effects. However, neither the time-course of signal enhancement nor the effect of continuous Mn2+ delivery on behaviour, particularly learning and memory, have been well-characterized. Here, we investigated the effect of MnCl2 dose and route of administration on a) spatial learning in the Morris Water Maze and b) tissue signal enhancement in the mouse brain. Even as early as 3 days after pump implantation, infusion of 25–50 mg/kg/day MnCl2 via osmotic pump produced signal enhancement as good as or better than that achieved 24 h after a single 50 mg/kg intraperitoneal injection. Neither route of delivery nor MnCl2 dose adversely affected spatial learning and memory on the water maze. However, especially at higher doses, mice receiving MnCl2 via osmotic pumps developed skin ulceration which limited the imaging window. With these findings, we provide recommendations for route and dose of MnCl2 to use for different study designs.

Type: Article
Title: Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroimage.2018.02.046
Publisher version: https://doi.org/10.1016/j.neuroimage.2018.02.046
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neuroimaging, Radiology, Nuclear Medicine & Medical Imaging, Neurosciences & Neurology, MEMRI, Osmotic pumps, Learning and memory, Behaviour, Toxicity, RESONANCE-IMAGING MEMRI, MAGNETIC-RESONANCE, IN-VIVO, INTENSITY NONUNIFORMITY, RAT-BRAIN, MICE, TOXICITY, DISEASE, TRANSPORT, CONTRAST
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre
URI: https://discovery.ucl.ac.uk/id/eprint/10060185
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