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