Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

Shao Ming Wang, Jung Yu C Hsu, Chiung Yuan Ko, Nai En Chiu, Wai Ming Kan, Ming Derg Lai, Ju Ming Wang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

After spinal cord injury, inflammatory reaction induces the aggregation of astrocytes to form a glial scar that eventually blocks axonal regeneration. Transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ) is a regulatory protein of genes responsive to inflammatory factors, but its role in glial scar formation after spinal cord injury remains unknown. By using a model of moderate spinal cord contusion injury at the mid-thoracic level, we found that C/EBPδ was expressed mostly in the reactive astrocytes bordering the lesion in wild-type mice from 7 days after the injury. C/EBPδ-deficient mice showed reduced glial scar formation, more residual white matter, and better motor function recovery compared with wild-type mice 28 days after the injury. Upon interleukin (IL)-1β stimulation in vitro, the increased expression of C/EBPδ in reactive astrocytes inhibited RhoA expression and, subsequently, the ability of astrocyte migration. However, these reactive astrocytes also produced an increased amount of matrix metalloproteinase-3, which promoted the migration of non-IL-1β-treated, inactive astrocytes. Although the involvement of other non-astroglial C/EBPδ cannot be entirely excluded, our studies suggest that astrocytic C/EBPδ is integral to the inflammatory cascades leading to glial scar formation after spinal cord injury.

Original languageEnglish
Pages (from-to)5912-5927
JournalMolecular Neurobiology
Volume53
Issue number9
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • Astrocyte migration
  • Astrogliosis
  • C/EBPδ
  • MMP-3
  • RhoA

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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