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Using Manganese-Enhanced MRI to Assess Optic Nerve Regeneration

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Book cover Axon Growth and Regeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1162))

Abstract

Experimental visual pathway lesion in the form of optic nerve (ON) crush or transection injury results in massive death of retinal ganglion cells (RGCs) and permanent loss of synaptic connections (Berkelaar et al., J Neurosci 14:4368–4374, 1994). Despite the fact that RGC axon regeneration is inhibited in a manner typical of other CNS lesions, the rodent ON injury model is one of the few models where robust axon regeneration has been achieved after therapeutic intervention (Berry et al., Restor Neurol Neurosci 26:147–174, 2008). However, assessment of the efficacy of therapeutic approaches in promoting ON regeneration has traditionally relied on histological methods, which necessitate the sacrifice of experimental animals and thus preclude longitudinal in vivo monitoring of individual subjects. Manganese-enhanced MRI (MEMRI) utilizes the paramagnetic properties and uptake and transport mechanisms of manganese ions (Mn2+) by neurons, thus enabling serial in vivo monitoring of the entire axonal projections (Sandvig et al., J Magn Reson Imaging 34:670–675, 2011; Thuen et al., J Magn Reson Imaging 4:492–500, 2005; Pautler et al., Magn Res Med 50:33–39, 2003; Saleem et al., Neurotechnique 34:685–700, 2000). The above properties of Mn2+ render MEMRI a highly suitable technique for assessment of ON regeneration after injury, especially with a view to in vivo monitoring of neuronal connectivity and axon-regenerative responses to treatment. In this chapter, we provide a generic protocol for ON lesioning and MEMRI application for assessment of ON regeneration in rodents.

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Acknowledgements

A number of people have made valuable contributions towards the protocols and techniques described in this chapter. The authors are grateful to Professor Martin Berry for expert training and advice in establishing the surgical protocols; Dr Christian Brekken, Dr Marte Thuen, and Professor Olav Haraldseth for their expertise in MRI; Dr Øystein Olsen for mathematical modeling; Dr Yrr Mørch and Professor Gudmund Skjåk-Bræk for the Mn2+-alginate microbeads; and Mrs Tina Bugge Pedersen for technical assistance. This work was supported by the Norwegian Research Council, Centre for Research-Based Innovation, Medical Imaging Laboratory (MI Lab), NTNU, Norway, and Functional Genomics (FUGE), Norway.

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Authors and Affiliations

  1. MI Lab and Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, 7489, Trondheim, Norway

    Ioanna Sandvig & Axel Sandvig

  2. Department of Neurosurgery, Umeå University Hospital, Umeå, Sweden

    Axel Sandvig

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  1. Ioanna Sandvig
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  2. Axel Sandvig
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Correspondence to Ioanna Sandvig .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA

    Andrew J. Murray

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Sandvig, I., Sandvig, A. (2014). Using Manganese-Enhanced MRI to Assess Optic Nerve Regeneration. In: Murray, A. (eds) Axon Growth and Regeneration. Methods in Molecular Biology, vol 1162. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0777-9_19

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  • DOI: https://doi.org/10.1007/978-1-4939-0777-9_19

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0776-2

  • Online ISBN: 978-1-4939-0777-9

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