Fibronectin EDA forms the chronic fibrotic scar after contusive spinal cord injury

John G. Cooper, Su Ji Jeong, Tammy L. McGuire, Sripadh Sharma, Wenxia Wang, Swati Bhattacharyya, John Varga, John A. Kessler*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is an impediment to axonal regeneration. Fibrotic scarring is characterized by the accumulation of fibronectin, collagen, and fibroblasts at the lesion site. The mechanisms regulating fibrotic scarring after SCI and its effects on axonal elongation and functional recovery are not well understood. In this study, we examined the effects of eliminating an isoform of fibronectin containing the Extra Domain A domain (FnEDA) on both fibrosis and on functional recovery after contusion SCI using male and female FnEDA-null mice. Eliminating FnEDA did not reduce the acute fibrotic response but markedly diminished chronic fibrotic scarring after SCI. Glial scarring was unchanged after SCI in FnEDA-null mice. We found that FnEDA was important for the long-term stability of the assembled fibronectin matrix during both the subacute and chronic phases of SCI. Motor functional recovery was significantly improved, and there were increased numbers of axons in the lesion site compared to wildtype mice, suggesting that the chronic fibrotic response is detrimental to recovery. Our data provide insight into the mechanisms of fibrosis after SCI and suggest that disruption of fibronectin matrix stability by targeting FnEDA represents a potential therapeutic strategy for promoting recovery after SCI.

Original languageEnglish (US)
Pages (from-to)60-68
Number of pages9
JournalNeurobiology of Disease
Volume116
DOIs
StatePublished - Aug 2018

Keywords

  • Fibronectin
  • Fibronectin EDA
  • Fibrosis
  • Gliosis
  • Matrix
  • Scarring
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology

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