Reactive Astrocytes in Glial Scar Attract Olfactory Ensheathing Cells Migration by Secreted TNF-a in Spinal Cord Lesion of Rat

PLoS ONE, 2009 · DOI: 10.1371/journal.pone.0008141 · Published: December 3, 2009

Simple Explanation

After spinal cord injury (SCI), glial scar formation hinders axon regeneration. Olfactory ensheathing cells (OECs) can migrate into the lesion site and induce axon regeneration. This study explores how OECs migrate to the glial scar. Reactive astrocytes in the glial scar release TNF-a, which attracts OECs. This attraction is mediated by TNFR1 receptors on OECs and involves the activation of ERK signaling pathways. This mechanism of attracting OECs to the glial scar is crucial for OECs-mediated axon regrowth beyond the spinal cord lesion site, suggesting a potential therapeutic strategy.

Study Duration

Not specified

Participants

Adult male Sprague-Dawley (170–200 g) rats

Evidence Level

Level 3; Experimental study in rat model

Key Findings

1
Glial scar tissue and reactive astrocyte-conditioned medium promote OECs migration in vitro.
2
Reactive astrocyte-derived TNF-a and its type 1 receptor TNFR1 expressed on OECs are responsible for promoting OECs migration.
3
TNF-a secreted by reactive astrocytes in glial scar attracts OECs migration in a rat spinal cord hemisection injury model.

Research Summary

This study investigates the mechanism by which olfactory ensheathing cells (OECs) migrate to the glial scar after spinal cord injury (SCI) in rats. The research found that reactive astrocytes in the glial scar release TNF-a, which attracts OECs migration through TNFR1 receptors and ERK signaling. These findings suggest that the attraction of OECs to the glial scar is crucial for axon regrowth and OECs-based treatment for CNS injury.

Practical Implications

Therapeutic Target

Targeting TNF-a signaling could enhance OECs migration to the lesion site, improving axon regeneration.

OECs Transplantation Strategies

Optimizing the timing and location of OECs transplantation to coincide with TNF-a gradients in the glial scar may improve outcomes.

Combination Therapies

Combining OECs transplantation with interventions that modulate reactive astrocyte activity and TNF-a release could further enhance axonal regeneration.

Study Limitations

1
Study performed only in a rat model; results may not directly translate to humans.
2
Focused solely on TNF-a; other factors influencing OECs migration were not investigated.
3
In vitro findings may not fully reflect the complex in vivo environment.

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