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  4. Artemin promotes functional long-distance axonal regeneration to the brainstem after dorsal root crush

Artemin promotes functional long-distance axonal regeneration to the brainstem after dorsal root crush

PNAS, 2015 · DOI: 10.1073/pnas.1502057112 · Published: May 12, 2015

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Spinal cord injuries often result in permanent paralysis due to the failure of axons to regenerate and reconnect with their original targets. This study investigates whether artemin (ARTN) can promote the regeneration of sensory axons to the brainstem after a dorsal root crush injury in rats. The researchers found that systemic artemin treatment promotes the regeneration of sensory axons to the brainstem, and importantly, these axons reestablish functional synapses with neurons in the cuneate nucleus. The study also demonstrates that GFRα3, a receptor for ARTN, is expressed on both myelinated and unmyelinated sensory neurons, which helps explain ARTN's ability to promote regeneration of both large and small sensory neurons.

Study Duration
6 Months
Participants
Adult rats
Evidence Level
Not specified

Key Findings

  • 1
    Systemic artemin (ARTN) treatment promotes the regeneration of crushed brachial sensory axons to the brainstem within 6 months after dorsal root (DR) crush.
  • 2
    ARTN treatment restores synaptic connectivity with the cuneate nucleus (CN) in the brainstem, indicating functional regeneration.
  • 3
    GFRα3 is expressed at comparable levels in myelinated and unmyelinated sensory neurons, providing a basis for the long-distance regeneration induced by ARTN.

Research Summary

This study demonstrates that systemic artemin (ARTN) treatment can promote the regeneration of sensory axons to the brainstem after a dorsal root crush injury in adult rats. The regenerated axons reestablish functional synapses with neurons in the cuneate nucleus, suggesting that ARTN can restore functional connectivity after spinal cord injury. The findings also show that GFRα3, a receptor for ARTN, is expressed on both myelinated and unmyelinated sensory neurons, supporting ARTN's ability to promote regeneration of both large and small sensory axons.

Practical Implications

Potential Therapy for Spinal Cord Injury

Artemin may represent a promising therapy for restoring sensory function after spinal cord injury due to its ability to promote targeted functional regeneration to the brainstem.

Understanding Axon Guidance

The study suggests that guidance cues persist in the adult CNS, and adult neurons retain some intrinsic ability to follow these cues to appropriate target areas.

Refining Therapeutic Delivery

The study indicates that a temporal pattern of trophic support might be more important than continuous activation of growth pathways.

Study Limitations

  • 1
    The DR crush model may have spared axons, which could contribute to the observed recovery.
  • 2
    The regeneration rate was slower than previously reported, potentially due to the absence of a conditioning lesion or the presence of CSPGs.
  • 3
    Behavioral tests for restoration of sensory input to the brainstem are not readily available.

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