Sensory axon regeneration: rebuilding functional connections in the spinal cord

Trends Neurosci, 2012 · DOI: 10.1016/j.tins.2011.10.006 · Published: March 1, 2012

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This review discusses recent progress in the regeneration of sensory axons after spinal cord injuries, focusing on how well these axons reconnect to their original targets. A key area of focus is the dorsal root entry zone (DREZ), a major barrier to sensory axon regeneration, and treatments that can help axons overcome this barrier are discussed. The review highlights the importance of not only promoting axon growth but also ensuring that the regenerating axons connect to the correct areas in the spinal cord to restore proper function.

Study Duration

Not specified

Participants

Animal models of spinal cord injury

Evidence Level

Review

Key Findings

1
Inactivation of inhibitory molecules like Nogo and chondroitin sulfate proteoglycans, as well as the administration of neurotrophic factors such as NGF, NT-3, GDNF, and artemin, can promote anatomical and functional regeneration across the DREZ.
2
The dorsal root crush model is a useful system for studying axon regeneration within the CNS, allowing manipulation of inhibitory components and assessment of functional regeneration with electrical recording.
3
Systemic ARTN treatments result in regeneration that is topologically specific, with different classes of sensory axons regenerating to their appropriate area in the spinal cord, while other treatments like sNgR and NGF may lead to disorganized projections.

Research Summary

The review focuses on recent advances in sensory axon regeneration, particularly the ability of sensory axons to reconnect with their original synaptic targets after spinal cord injury. It discusses the dorsal root entry zone (DREZ) as a major barrier to regeneration and highlights various experimental treatments that promote anatomical and functional regeneration across this barrier. The review emphasizes the importance of topographic specificity in regeneration, where regenerating axons project back to their appropriate target areas within the spinal cord to restore proper function.

Practical Implications

Therapeutic Strategies

Development of therapies that target both the inhibitory environment of the CNS and the intrinsic growth state of neurons to promote effective axon regeneration.

Targeted Delivery

Use of localized viral expression of neurotrophic factors and guidance molecules to direct regenerating axons to appropriate target areas in the spinal cord.

Functional Restoration

Understanding the mechanisms underlying topographic specificity in axon regeneration to develop strategies for promoting functionally appropriate neural circuits after spinal cord injury.

Study Limitations

1
The review primarily focuses on animal models of spinal cord injury, and the translation of these findings to human patients remains a challenge.
2
Specificity of regeneration remains an issue with certain treatments, as some therapies may lead to disorganized axonal projections and require further refinement.
3
The long-term effects of different regeneration strategies and the potential for synaptic refinement and plasticity need further exploration.

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