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Progranulin expression is upregulated after spinal contusion in mice

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Abstract

Progranulin (proepithelin) is a pleiotropic growth-factor associated with inflammation and wound repair in peripheral tissues. It also has been implicated in the response to acute traumatic brain injury as well as to chronic neurodegenerative diseases. To determine whether changes in progranulin expression also accompany acute spinal cord injury, C57BL/6 mice were subjected to mid-thoracic (T9 level) contusion spinal cord injury and analyzed by immunohistochemical and biochemical methods. Whereas spinal cord sections prepared from non-injured laminectomy control animals contained low basal levels of progranulin immunoreactivity in gray matter, sections from injured animals contained intense immunoreactivity throughout the injury epicenter that peaked 7–14 days post injury. Progranulin immunoreactivity colocalized with myeloid cell markers CD11b and CD68, indicating that expression increased primarily in activated microglia and macrophages. Immunoblot analysis confirmed that progranulin protein levels rose after injury. On the basis of quantitative polymerase chain reaction analysis, increased protein levels resulted from a tenfold rise in progranulin transcripts. These data demonstrate that progranulin is dramatically induced in myeloid cells after experimental spinal cord injury and is positioned appropriately both spatially and temporally to influence recovery after injury.

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Acknowledgments

We thank Dr. Mariano Viapiano (Department of Neurosurgery) for guidance with imaging methods. This work was supported by The Ohio State University Neuroscience Signature Program (S.K.K., L.B.J., J.K.), National Institute for Neurological Disorders and Stroke (P.G.P.), Neuroscience Core Center (NS045758), and The Ohio State Center for Brain and Spinal Cord Repair.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, The Ohio State University College of Medicine, Columbus, OH, 43210, USA

    Swati B. Naphade & Jeff Kuret

  2. Department of Molecular Virology, Immunology and Medical Genetics, Center for Brain and Spinal Cord Repair, The Ohio State University College of Medicine, Columbus, OH, 43210, USA

    Kristina A. Kigerl & Phillip G. Popovich

  3. Department of Cell Biology and Physiology, Center for Brain and Spinal Cord Repair, The Ohio State University College of Medicine, Columbus, OH, 43210, USA

    Lyn B. Jakeman

  4. Department of Neurology, Center for Brain and Spinal Cord Repair, The Ohio State University College of Medicine, Columbus, OH, 43210, USA

    Sandra K. Kostyk

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  1. Swati B. Naphade
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Correspondence to Jeff Kuret.

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Naphade, S.B., Kigerl, K.A., Jakeman, L.B. et al. Progranulin expression is upregulated after spinal contusion in mice. Acta Neuropathol 119, 123–133 (2010). https://doi.org/10.1007/s00401-009-0616-y

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  • DOI: https://doi.org/10.1007/s00401-009-0616-y

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