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

Dulcie A Vousden; Elizabeth Cox; Rylan Allemang-Grand; Christine Laliberté; Lily R Qiu; Zsuzsa Lindenmaier; Brian J Nieman; Jason P Lerch

doi:10.1016/j.neuroimage.2018.02.046

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

Neuroimage. 2018 Jun:173:411-420. doi: 10.1016/j.neuroimage.2018.02.046. Epub 2018 Mar 2.

Authors

Dulcie A Vousden¹, Elizabeth Cox², Rylan Allemang-Grand³, Christine Laliberté², Lily R Qiu⁴, Zsuzsa Lindenmaier³, Brian J Nieman⁵, Jason P Lerch³

Affiliations

¹ Mouse Imaging Centre, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada. Electronic address: d.vousden@alum.utoronto.ca.
² Mouse Imaging Centre, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
³ Mouse Imaging Centre, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada.
⁴ Mouse Imaging Centre, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
⁵ Mouse Imaging Centre, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada; Department of Medical Biophysics, University of Toronto, 101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada; Ontario Institute for Cancer Research, MaRS Centre, 661 University Ave, Suite 510, Toronto, ON, M5G 0A3, Canada.

PMID: 29505831
DOI: 10.1016/j.neuroimage.2018.02.046

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.

Keywords: Behaviour; Learning and memory; MEMRI; Osmotic pumps; Toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects*
Chlorides / administration & dosage*
Chlorides / toxicity
Image Enhancement / methods
Infusion Pumps, Implantable
Magnetic Resonance Imaging / methods*
Male
Manganese Compounds / administration & dosage*
Maze Learning / drug effects*
Mice
Skin Ulcer / chemically induced*

Substances

Chlorides
Manganese Compounds
manganese chloride