Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes
Open accessAbstract
The extracellular matrix (ECM) molecules chondroitin-6-sulfate proteoglycan (CS-PG) and cytotactin/tenascin (CT), present on subpopulations of astroglia or their precursors during development, can inhibit neurite outgrowth in vitro. However, it is not known whether these molecules are expressed within the mature CNS following injury, where they could contribute to regenerative failure. Thus, the expression of various ECM molecules that affect axon growth was examined in areas of reactive gliosis caused by implanting a piece of nitrocellulose into the cortex of neonatal and adult animals. The expression of these molecules was compared to the amount of neurite outgrowth that occurred in vitro when the damaged CNS tissue from animals of various ages was removed intact and used as a substrate in explant culture. The results demonstrate that the growth-promoting molecules laminin, collagen type IV, and fibronectin were present around the implant in all experimental groups. In comparison, CS-PG and CT were present within and around the area of the lesion only in adult animals. In vivo, these molecules were colocalized with intensely glial fibrillary acidic protein (GFAP)-positive astrocytes in and immediately adjacent to the scar, but not with other equally intensely GFAP- positive astrocytes in the cortex away from the site of injury. CT and CS-PG were present in gray matter areas of the cortex that had been directly damaged during the implant procedure and in the corpus callosum when lesioned during implantation. In vitro, the glial tissue removed from the lesion site of neonatal animals supported neurite outgrowth, while scars removed from adult animals did not. The inability of the adult glial scar tissue to support neurite outgrowth was best correlated with the expression of CS-PG and CT, suggesting that these molecules may be involved in limiting the growth of regenerating axons in the CNS after injury.
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One of the main features of the ECM and PNNs is to restrict the formation of neurites and their synapses while protecting neurons towards harmful substances or events.
“Several studies of the recent years have shown that one of the main features of the ECM and PNNs is to restrict the formation of neurites42 and their synapses with concurrent protection of neurons towards harmful substances or events43.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [42]
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- Authors
- McKeon, R., Schreiber, R., Rudge, J., & Silver, J.
- Affiliations
- Case Western Reserve University (US)
- ORCID
- Silver, J
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1991-11-01
- Volume
- 11
- Issue
- 11
- Pages
- 3398-3411
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6575543
- OpenAlex
- W2097530133
- Cited by
- 1,188
- References
- 38
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 22 · 2023: 18 · 2022: 30 · 2021: 50 · 2020: 33 · 2019: 25 · 2018: 23 · 2017: 29 · 2016: 30 · 2015: 41 · 2014: 46 · 2013: 34 · 2012: 51
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (T32NS007118, NS 25713)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- glial scar, reactive astrocytes, neurite outgrowth, extracellular matrix, central nervous system injury, axon regeneration, laminin, type IV collagen, fibronectin, glial fibrillary acidic protein, explant culture, corpus callosum lesions
- MeSH terms
- Animals, Animals, Newborn, Astrocytes, Collodion, Extracellular Matrix, Glial Fibrillary Acidic Protein, Gliosis, Glycoproteins, Immunohistochemistry, Microscopy, Electron, Neural Inhibition, Neuroglia, Proteoglycans, Rats, Inbred Strains, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Neurites, Tenascin, Prostheses and Implants, Lectins, C-Type, Rats, Aggrecans
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