Propagation of spreading depression inversely correlates with cortical myelin content

Authors

  • Doron Merkler MD,

    Corresponding author
    1. Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany
    • Department of Neuropathology, Robert-Koch-Str. 40, 37099 Göttingen, Germany
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    • D.M. and F.K. contributed equally to this work.

  • Florian Klinker MD,

    1. Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
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    • D.M. and F.K. contributed equally to this work.

  • Tanja Jürgens MSc,

    1. Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany
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  • Raoul Glaser MD,

    1. Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
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  • Walter Paulus MD,

    1. Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
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  • Bastian G. Brinkmann MD,

    1. Research Group “Molecular Neurology,” Department of Neurogenetics, Max Planck Institute for Experimental Medicine, Göttingen, Germany
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  • Michael W. Sereda MD,

    1. Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
    2. Research Group “Molecular Neurology,” Department of Neurogenetics, Max Planck Institute for Experimental Medicine, Göttingen, Germany
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  • Christine Stadelmann-Nessler MD,

    1. Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany
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  • Rubem C. A. Guedes PhD,

    1. Department of Nutrition, Universidade Federal de Pernambuco, Recife, PE, Brazil
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  • Wolfgang Brück MD,

    1. Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany
    2. Institut für Multiple-Sklerose-Forschung, University Medical Center Göttingen and Gemeinnützige Hertie-Stiftung, Göttingen, Germany
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  • David Liebetanz MD

    1. Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
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  • Potential conflict of interest: Nothing to report.

Abstract

Objective

Cortical myelin can be severely affected in patients with demyelinating disorders of the central nervous system. However, the functional implication of cortical demyelination remains elusive. In this study, we investigated whether cortical myelin influences cortical spreading depression (CSD).

Methods

CSD measurements were performed in rodent models of toxic and autoimmune induced cortical demyelination, in neuregulin-1 type I transgenic mice displaying cortical hypermyelination, and in glial fibrillary acidic protein–transgenic mice exhibiting pronounced astrogliosis.

Results

Cortical demyelination, but not astrogliosis or inflammation per se, was associated with accelerated CSD. In contrast, hypermyelinated neuregulin-1 type I transgenic mice displayed a decelerated CSD propagation.

Interpretation

Cortical myelin may be crucially involved in the stabilization and buffering of extracellular ion content that is decisive for CSD propagation velocity and cortical excitability, respectively. Our data thus indicate that cortical involvement in human demyelinating diseases may lead to relevant alterations of cortical function. Ann Neurol 2009;66:355–365

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