Oncostatin M Reduces Lesion Size and Promotes Functional Recovery and Neurite Outgrowth After Spinal Cord Injury Helena Slaets & Sofie Nelissen & Kris Janssens & Pia M. Vidal & Evi Lemmens & Piet Stinissen & Sven Hendrix & Niels Hellings Received: 13 January 2014 /Accepted: 15 June 2014 /Published online: 5 July 2014 # Springer Science+Business Media New York 2014 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 re- sponses. 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 re- covery 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 infiltra- tion. Thus, OSM limits secondary damage after CNS trauma. In vitro viability assays demonstrated that OSM protects pri- mary 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 in- creases 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. Keywords SCI . OSM . Neuroinflammation . Neuroprotection Introduction Spinal cord injury (SCI) is a devastating condition caused by trauma to the spinal cord, which is characterized by the loss of motor, sensory, and autonomous functions below the lesion site [1]. After the initial damage, a neuroinflammatory re- sponse is set in motion that induces secondary cell death in the tissue surrounding the original site of injury. This second- ary damage continues in the days and weeks following SCI, aggravating neurological dysfunction. The neuroinflammatory response is characterized by local glia activation, infiltration of leukocytes, and synthesis of cytokines and chemokines [2, 3]. Treatment of SCI starts with restraining the spine and control- ling the inflammatory response to prevent further damage. High-dose corticosteroids may improve outcome if given within 6 h of injury. However, the improvement is small and comes with the risk of infection or sepsis due to general immune suppression [4]. In addition, certain aspects of the neuroinflammatory response are beneficial and even neces- sary to induce wound healing. In order to design adequate treatments for SCI, it is of crucial importance to understand the role of the different cytokines produced during the neuroinflammatory response to injury [5]. Among the cytokines produced at the lesion site, members of the interleukin (IL)-6 cytokines play a diverse role. The IL- Electronic supplementary material The online version of this article (doi:10.1007/s12035-014-8795-5) contains supplementary material, which is available to authorized users. Niels Hellings and Sven Hendrix are equally contributing senior authors to this work. H. Slaets : K. Janssens : P. Stinissen : N. Hellings (*) Biomedical Research Institute, Hasselt University, School of Life Sciences, Transnational University Limburg, Diepenbeek, Belgium e-mail: niels.hellings@uhasselt.be S. Nelissen : P. M. Vidal : E. Lemmens : S. Hendrix (*) Department of Morphology and Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium e-mail: sven.hendrix@uhasselt.be S. Nelissen Cell Physiology, Biomedical Research Institute, Hasselt University and Transnational University Limburg, Agoralaan Gebouw C, 3590 Diepenbeek, Belgium Mol Neurobiol (2014) 50:1142–1151 DOI 10.1007/s12035-014-8795-5