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

Glia, 2008 · DOI: 10.1002/glia.20721 · Published: November 15, 2008

Simple Explanation

When the central nervous system (CNS) is injured, cells called astrocytes react and form a glial scar. This scar acts like a barrier, preventing nerve fibers (axons) from regrowing. This study created a model of this scar in the lab to better understand how it forms and how to overcome it. The model combines mechanical injury (stretch) and interaction with other cells (meningeal fibroblasts) to mimic the conditions after CNS trauma. The astrocytes in the model showed changes similar to those seen in real scars, including increased production of certain proteins. The model was tested by growing nerve cells on it and observing their growth. The nerve cells grew poorly on the scar model, demonstrating its ability to mimic the inhibitory effects of a real glial scar. This model can be used to test potential treatments to promote nerve regeneration after CNS injuries.

Study Duration

4 weeks

Participants

Newborn rat cortices, E15 rat dorsal root ganglion (DRG), E18 or postnatal day 4 (P4) rat spinal cords or motor cortex-enriched cortices

Evidence Level

In vitro study

Key Findings

1
Mechanical stretch and co-culture with meningeal cells induced astrocyte reactivity, including stellation, clustering, and GFAP accumulation.
2
The in vitro scar model exhibited increased expression of scar-associated markers such as phosphacan, neurocan, and tenascins.
3
Neurite growth from various CNS neuronal populations was significantly reduced on the scar-like cultures, indicating growth inhibition.

Research Summary

This study introduces a novel in vitro model of the glial scar, generated by combining mechanical trauma and co-culture with meningeal cells using highly differentiated astrocytes. The model effectively mimics key aspects of scar formation, including morphological signs of astrocyte reactivity, increased expression of GFAP and scar-associated markers, and widespread inhibition of axonal regeneration. The in vitro scar model should be valuable for examining mechanisms underlying scar formation and for assessing potential treatments to improve regeneration after CNS injury.

Practical Implications

Understanding Scar Formation

The model can be used to investigate the mechanisms regulating astrocyte reactivity and inhibitory protein expression.

Therapeutic Development

The model provides a platform for testing potential therapeutics aimed at improving regeneration after CNS injury.

Personalized Medicine

The model can help understand why different neuronal populations respond differently to the glial scar, which may help tailor treatments for specific injuries.

Study Limitations

1
The model is an in vitro system and may not fully replicate the complexity of the in vivo glial scar.
2
The model focuses on astrocytes and meningeal fibroblasts, and may not fully represent the contributions of other cell types involved in scar formation.
3
The study examined short-term co-cultures, and the long-term effects of the scar model on neurite growth were not assessed.

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