Volume 31 Issue 10 - November 15, 2019 PDF
Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury
Shao-Ming Wang1 & Jung-Yu C. Hsu2 & Chiung-Yuan Ko6,7 & Nai-En Chiu3 & Wai-Ming Kan3 & Ming-Derg Lai1 & Ju-Ming Wang1,4,5,*
1 Institute of Basic Medical Sciences College of Medicine , National Cheng Kung University
2 Department of Cell Biology and Anatomy College of Medicine , National Cheng Kung University
3 Department of Pharmacology College of Medicine , National Cheng Kung University
4 Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University
5 Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University
6 Center for Neurotrauma and Neuroregeneration, College of Medical Science and Technology, Taipei Medical University
7 Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University
Font Enlarge
Spinal cord injury (SCI) refers to injury to the spinal cord that causes devastating clinical conditions that can result in permanent disabilities. According to the WHO, worldwide, it is estimated that between 250,000 and 500,000 people suffer a spinal cord injury every year (1). After SCI, disrupted blood vessels in the lesion allow the infiltration of inflammatory cells and the release of inflammatory cytokines; this not only exacerbates the extent of the primary injury but also induces astrocyte reactivity and glial scar formation. Some studies have suggested that glial scar formation can block and inhibit neuronal regeneration and then cause secondary damage. However, currently, the biological function of astrocytes and the mechanism leading to the formation of glial scars is not clear. Transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ) belongs to the CCAAT/enhancer-binding protein (C/EBP) family. Our previous studies suggested that C/EBPδ is involved in neuro-inflammatory responses and contributes to brain degeneration progress (2-4).

In a recent study, we further provide novel evidence demonstrating that C/EBPδ promotes glial scar formation and plays dual roles in astrocyte migration after SCI. We showed that C/EBPδ was expressed in reactive astrocytes along the lesion border and C/EBPδ−/− mice exhibited reduced glial scar, more residual white matter, and better motor function recovery than wild-type mice after the injury. In response to IL-1β stimulation, increased C/EBPδ repressed RhoA transcription and thus inhibited astrocyte motility. Meanwhile, C/EBPδ also enhanced the transcription and secretion of MMP-3, which selectively promoted the migration of non-IL-1β-treated, inactive astrocytes (Figure 1). Together, our results suggest that C/EBPδ can modulate astrocyte motility and is integral to glial scar formation after SCI.
Figure 1.  A schematic diagram illustrates the proposed model for the modulatory effect of C/EBPδ on astrocyte migration and glial scar formation after SCI. In response to the injury, inflammatory cytokine IL-1β released in the lesion epicenter activates astrocytic expression of C/EBPδ, which in turn inhibits RhoA expression and thus impedes the migration of the astrocytes located along the lesion border. Simultaneously, C/EBPδ upregulates astrocytic expression of MMP-3. Diffusion of MMP-3 promotes the migration of neighboring astrocytes, particularly those in the penumbral region between the lesion border and less injured cord tissue.

  1. http://www.who.int/mediacentre/news/releases/2013/spinal-cord-injury-20131202/en/
  2. Neurobiol Aging. 2012 Feb;33(2):422.e11-25.
  3. Neurobiol Aging. 2015 Mar;36(3):1356-68.
  4. Mol Neurobiol. 2015 Feb;51(1):370-82.
< Previous
Next >
Copyright National Cheng Kung University