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Spinal cord injury-induced lesional expression of the repulsive guidance molecule (RGM)

Authors

  • Jan M. Schwab,

    1. Institute of Brain Research, Eberhard-Karls-University Tuebingen, School of Medicine, Calwer Str. 3, D-72076 Tuebingen, Germany
    2. CNRS UMR 7102, Université Pierre et Marie Curie, Equipe Développement Neuronal, Paris, France
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    • Present address: Brigham and Women's Hospital, Center for Experimental Therapeutics, Harvard Medical School, Boston, 02115 MA, USA.

    • *

      J.M.S. and S.C contributed equally to this work.

  • Sabine Conrad,

    1. Institute of Brain Research, Eberhard-Karls-University Tuebingen, School of Medicine, Calwer Str. 3, D-72076 Tuebingen, Germany
    2. Experimental Tissue Engineering, Institute of Anatomy, University of Tuebingen, Germany
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    • *

      J.M.S. and S.C contributed equally to this work.

  • Philippe P. Monnier,

    1. Division of Cellular and Molecular Biology, Toronto Western Research Institute, University of Toronto, Ontario Canada
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  • Sylvie Julien,

    1. Experimental Ophthalmology, Eberhard-Karls University Tuebingen, Germany
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  • Bernhard K. Mueller,

    1. CNS Research, Abbott GmbH and Company KG, Ludwigshafen, Germany
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  • Hermann J. Schluesener

    1. Institute of Brain Research, Eberhard-Karls-University Tuebingen, School of Medicine, Calwer Str. 3, D-72076 Tuebingen, Germany
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Dr Jan M. Schwab, at †present address below.
E-mail: jschwab@zeus.bwh.harvard.edu

Abstract

The repulsive guidance molecule (RGM) is involved in the formation of the central nervous system (CNS) during development by modulating guidance of growing axons. However, a role of RGM in CNS injury remains to be established. We studied the expression of RGM in the spinal cord of rats with spinal cord injury (SCI). After SCI, RGM+ cells accumulated in lesions and peri-lesional areas. During the first days after SCI, RGM expression was confined to neurons, ballooned neurite fibers/retraction bulbs, smooth muscle/endothelial cells, and to leucocytes infiltrating the lesion. Lesional RGM expression was frequently confined to hypertrophic β-APP+ and RhoA+ neurites/retraction bulbs. With maturation of the lesion, we observed RGM expression by components of the developing scar tissue (cicatrix), such as fibroblastoid cells, reactive astrocytes and in addition a pronounced extracellular RGM deposition resembling neo-laminae. Frequent RGM+, RhoA+ coexpression by lesional retraction bulbs represent first preliminary evidence of RGM to exert growth inhibitory effects by the second messenger system RhoA. To date, RGM is one of the most potent axonal growth inhibitors identified and present in axonal growth impediments (i) oligodendrocytes; (ii) the plexus choroideus and (iii) components of the developing scar.

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