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  4. Motor Axonal Regeneration following Cord Transection

Motor Axonal Regeneration following Cord Transection

The Journal of Neuroscience, 2012 · DOI: 10.1523/JNEUROSCI.3858-12.2012 · Published: November 7, 2012

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Lu et al. (2012) used a rat lateral mid-cervical hemisection model and demonstrated that a combinatorial treatment strategy resulted in motor axon regeneration. This combinatorial strategy included administration of the cell-permeable dibutyryl cAMP in brainstem reticular motor nuclei, bone marrow stromal cell grafts in the lesion site, and brain-derived neurotrophic factor (BDNF) gradients beyond the lesion site. To remove the contribution of the intact reticulospinal tract, which is spared following lateral hemisection, Lu et al. (2012) also tested their optimal full combinatorial treatment in a rat upper thoracic full-transection model. Because the majority of motor assessments are inappropriate to use in full-transection models, Lu et al. (2012) used open-field locomotion, assessed with a Beattie–Basso–Bresnahan (BBB) score. The authors explored this possibility by using a five-point spasticity scale in response to a standardized stretch/rub maneuver and found that BDNF treatment below the transection site was associated with heightened spasticity. Thus, the combined therapeutic strategy promoted regeneration in both lesion models and was associated with either worsened motor function or enhanced spasticity.

Study Duration
Not specified
Participants
Rats in lateral mid-cervical hemisection and upper thoracic full-transection models
Evidence Level
Not specified

Key Findings

  • 1
    A combinatorial treatment strategy promoted axonal regeneration in both hemisection and full transection models.
  • 2
    In the hemisection model, despite axonal regeneration, motor outcomes worsened.
  • 3
    In the full transection model, the same combinatorial treatment improved BBB motor outcomes, but resection of regenerated fibers did not abolish gained function.

Research Summary

Lu et al. (2012) provide an important contribution to the field of neuroscience in demonstrating axonal regeneration following partial and complete cord transection. Perhaps surprisingly, this regeneration of a descending motor tract is not associated with improvements in motor function, highlighting the complexity of axonal regeneration and how it relates to restoring motor function. Given that there are no current therapeutic interventions for treatment of SCI, there is an exigent need to further investigate regenerative therapies and assess how regeneration relates to functional recovery.

Practical Implications

Complexity of Functional Recovery

Simply promoting axonal regeneration may not be sufficient to restore motor function after spinal cord injury; other factors like synapse formation and appropriate tract regeneration are crucial.

Potential Harmful Consequences

Strategies designed to improve motor function can also promote plasticity of unintended targets, leading to harmful consequences like increased spasticity, which may mask the beneficial effects of axonal regeneration.

Comprehensive Assessment

Outcome assessments for regenerative treatment strategies should include evaluation of pain behavior, as relieving pain is a high priority for individuals with SCI and is frequently overlooked.

Study Limitations

  • 1
    The study could not determine whether observed synaptic structures were functional.
  • 2
    The combinatorial strategy targeted regeneration only of the reticulospinal tract; corticospinal and rubrospinal regeneration were not assessed.
  • 3
    The treatment resulted in hyperexcitability of spinal circuitry.

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