Glucocorticoid Regulation of Ependymal Glia and Regenerative Potential after Spinal Cord Injury: Glucocorticoid inhibition of neural regeneration

Craig M. Nelson, Han Lee, Randall G. Krug, Aichurok Kamalova, Nicolas N. Madigan, Karl J. Clark, Vanda A. Lennon, Anthony J. Windebank, John R Henley

Research output: Contribution to journalArticlepeer-review

Abstract

Following injury, the mammalian spinal cord forms a glial scar and fails to regenerate. In contrast, spinal cord tissue of vertebrate fish regenerates and restores function. Cord transection in zebrafish (Danio rerio) initially causes paralysis and neural cell death, with subsequent ependymal glial proliferation, extension of bipolar glia across the lesion, and neurogenesis. Axons extending from spared and nascent neurons along trans-lesional glial bridges restore functional connectivity. Here we report that glucocorticoids directly target the regeneration supporting changes in ependymal glia to inhibit neural repair. This effect is independent of hematogenic immune cells or microglia. Furthermore, glucocorticoid receptor signaling in ependymal glia is inversely regulated in rat models of spinal cord injury compared to zebrafish. The blockade of neural regeneration by glucocorticoids via a direct effect on ependymal glia has important clinical implications concerning the putative therapeutic benefit of corticosteroids in early management of spinal cord injury.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - May 25 2018

Keywords

  • Ependymal glia
  • Glial bridge
  • Glucocorticoid signaling
  • Neural regeneration
  • Nr3c1
  • Spinal cord injury

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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