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Fibronectin EDA forms the chronic fibrotic scar after contusive spinal cord injury
- Source :
- Neurobiology of Disease, Vol 116, Iss, Pp 60-68 (2018)
- Publication Year :
- 2018
-
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.
- Subjects :
- 0301 basic medicine
Gene isoform
Male
Pathology
medicine.medical_specialty
Spinal cord injury
Matrix (biology)
Article
lcsh:RC321-571
03 medical and health sciences
Cicatrix
Mice
0302 clinical medicine
Fibrosis
medicine
Animals
Gliosis
Fibronectin
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Spinal Cord Injuries
Mice, Knockout
biology
Matrix
business.industry
Regeneration (biology)
Recovery of Function
Functional recovery
medicine.disease
Fibronectins
Mice, Inbred C57BL
030104 developmental biology
Neurology
Fibronectin EDA
biology.protein
Female
medicine.symptom
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1095953X
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Neurobiology of disease
- Accession number :
- edsair.doi.dedup.....ad0fa6413e7406b69a625927b3c9ed02