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Oncostatin M Reduces Lesion Size and Promotes Functional Recovery and Neurite Outgrowth After Spinal Cord Injury

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Abstract

The family of interleukin (IL)-6 like cytokines plays an important role in the neuroinflammatory response to injury by regulating both neural as well as immune responses. Here, we show that expression of the IL-6 family member oncostatin M (OSM) and its receptor is upregulated after spinal cord injury (SCI). To reveal the relevance of increased OSM signaling in the pathophysiology of SCI, OSM was applied locally after spinal cord hemisection in mice. OSM treatment significantly improved locomotor recovery after mild and severe SCI. Improved recovery in OSM-treated mice was associated with a reduced lesion size. OSM significantly diminished astrogliosis and immune cell infiltration. Thus, OSM limits secondary damage after CNS trauma. In vitro viability assays demonstrated that OSM protects primary neurons in culture from cell death, suggesting that the underlying mechanism involves direct neuroprotective effects of OSM. Furthermore, OSM dose-dependently promoted neurite outgrowth in cultured neurons, indicating that the cytokine plays an additional role in CNS repair. Indeed, our in vivo experiments demonstrate that OSM treatment increases plasticity of serotonergic fibers after SCI. Together, our data show that OSM is produced at the lesion site, where it protects the CNS from further damage and promotes recovery.

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Acknowledgments

This work was financially supported by grants from NEURONET Methusalem and from the Flemish Fund for Scientific Research (FWO Vlaanderen) to H.S (1.5.121.12 N), to N.H. (G04441N), and to S.H. (G.0834.11 N, G.0389.12 N, G0A1413N).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Biomedical Research Institute, Hasselt University, School of Life Sciences, Transnational University Limburg, Diepenbeek, Belgium

    Helena Slaets, Kris Janssens, Piet Stinissen & Niels Hellings

  2. Department of Morphology and Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium

    Sofie Nelissen, Pia M. Vidal, Evi Lemmens & Sven Hendrix

  3. Cell Physiology, Biomedical Research Institute, Hasselt University and Transnational University Limburg, Agoralaan Gebouw C, 3590, Diepenbeek, Belgium

    Sofie Nelissen

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  1. Helena Slaets
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Correspondence to Sven Hendrix or Niels Hellings.

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Niels Hellings and Sven Hendrix are equally contributing senior authors to this work.

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Supplementary Fig. 1

Kinetics of mRNA expression of LIF, IL-6, CNTF and their specific receptor subunits after spinal cord injury. RNA was isolated from a standardized piece of 1 cm around the spinal cord lesion, at indicated time points following hemisection (SCI) or laminectomy without touching the spinal cord (sham). Quantitative PCR revealed upregulation of LIF (a) and IL-6 expression (b) but no induction of CNTF (c) or the specific receptor subunits (d, e, f) after injury. * indicates P<0,05; ** indicates P<0,01 compared to levels in untouched mice (0h) as analyzed by Kruskall Wallis test followed by Dunn’s multiple comparison test. (GIF 33 kb)

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Slaets, H., Nelissen, S., Janssens, K. et al. Oncostatin M Reduces Lesion Size and Promotes Functional Recovery and Neurite Outgrowth After Spinal Cord Injury. Mol Neurobiol 50, 1142–1151 (2014). https://doi.org/10.1007/s12035-014-8795-5

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