A new in vitro model of the glial scar inhibits axon growth

Ina B. Wanner, Andres Deik, Miguel Torres, Andrew Rosendahl, Joseph T. Neary, Vance Lemmon, John Bixby

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Astrocytes respond to central nervous system (CNS) injury with reactive astrogliosis and participate in the formation of the glial scar, an inhibitory barrier for axonal regeneration. Little is known about the injury-induced mechanisms underlying astrocyte reactivity and subsequent development of an axon-inhibitory scar. We combined two key aspects of CNS injury, mechanical trauma and co-culture with meningeal cells, to produce an in vitro model of the scar from cultures of highly differentiated astrocytes. Our model displayed widespread morphological signs of astrocyte reactivity, increases in expression of glial fibrillary acidic protein (GFAP), and accumulation of GFAP in astrocytic processes. Expression levels of scar-associated markers, phosphacan, neurocan, and tenascins, were also increased. Importantly, neurite growth from various CNS neuronal populations was significantly reduced when neurons were seeded on the scar-like cultures, compared with growth on cultures of mature astrocytes. Quantification of neurite growth parameters on the scar model demonstrated significant reductions in neuronal adhesion and neurite lengths. Interestingly, neurite outgrowth of postnatal neurons was reduced to a greater extent than that of embryonic neurons, and outgrowth inhibition varied among neuronal populations. Scar-like reactive sites and neurite-inhibitory patches were found throughout these cultures, creating a patchwork of growth-inhibitory areas mimicking a CNS injury site. Thus, our model showed relevant aspects of scar formation and produced widespread inhibition of axonal regeneration; it should be useful both for examining mechanisms underlying scar formation and to assess various treatments for their potential to improve regeneration after CNS injury.

Original languageEnglish
Pages (from-to)1691-1709
Number of pages19
JournalGLIA
Volume56
Issue number15
DOIs
StatePublished - Dec 1 2008

Fingerprint

Neuroglia
Cicatrix
Axons
Nervous System Trauma
Astrocytes
Growth
Neurites
Central Nervous System
Regeneration
Glial Fibrillary Acidic Protein
Neurons
Neurocan
Class 5 Receptor-Like Protein Tyrosine Phosphatases
Tenascin
In Vitro Techniques
Wounds and Injuries
Coculture Techniques
Population
Catalytic Domain

Keywords

  • Astrogliosis
  • CNS injury
  • Fibroblast
  • Inhibition
  • Meningeal cells
  • Neurite outgrowth
  • Proteoglycans
  • Reactive astrocyte
  • Spinal cord injury
  • Tenascin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Wanner, I. B., Deik, A., Torres, M., Rosendahl, A., Neary, J. T., Lemmon, V., & Bixby, J. (2008). A new in vitro model of the glial scar inhibits axon growth. GLIA, 56(15), 1691-1709. https://doi.org/10.1002/glia.20721

A new in vitro model of the glial scar inhibits axon growth. / Wanner, Ina B.; Deik, Andres; Torres, Miguel; Rosendahl, Andrew; Neary, Joseph T.; Lemmon, Vance; Bixby, John.

In: GLIA, Vol. 56, No. 15, 01.12.2008, p. 1691-1709.

Research output: Contribution to journalArticle

Wanner, IB, Deik, A, Torres, M, Rosendahl, A, Neary, JT, Lemmon, V & Bixby, J 2008, 'A new in vitro model of the glial scar inhibits axon growth', GLIA, vol. 56, no. 15, pp. 1691-1709. https://doi.org/10.1002/glia.20721
Wanner IB, Deik A, Torres M, Rosendahl A, Neary JT, Lemmon V et al. A new in vitro model of the glial scar inhibits axon growth. GLIA. 2008 Dec 1;56(15):1691-1709. https://doi.org/10.1002/glia.20721
Wanner, Ina B. ; Deik, Andres ; Torres, Miguel ; Rosendahl, Andrew ; Neary, Joseph T. ; Lemmon, Vance ; Bixby, John. / A new in vitro model of the glial scar inhibits axon growth. In: GLIA. 2008 ; Vol. 56, No. 15. pp. 1691-1709.
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