Regenerative medicine offers hope in spinal cord injury

Spinal cord injury (SCI) can be a catastrophic event for the individual. Traditionally, such injuries were viewed as permanent, irreversible neurological dysfunction, but over time research has shown some neuroplastic capability of the injured adult mammalian spinal cord. However, spontaneous functional recovery post-SCI is very modest.

The peripheral nervous system (PNS), in contrast, is more robust in its capacity to regenerate following damage. Among the strategies to utilize elements of the PNS for regeneration of spinal cord, neurotization - the rerouting of intact peripheral nerves originating from spinal segments above the site of injury - has previously been studied and even applied clinically. Functional improvements after spinal cord injury (SCI) have been reported anecdotally following neurotization, but the underlying mechanisms have been poorly understood.

Using a rat model for spinal cord injury, Scientists at Harvard have shown significant functional recovery in neurotized animals versus controls. In addition to limited reinnervation in the target muscles, neurotized animals demonstrated multiparameters of neural reorganization in the distal lumbar cord. The findings are published in the May issue of Regenerative Medicine1 published by Future Medicine.

Dr Yang D. Teng, Director of the Laboratories of Spinal Cord injury and Neural Stem Cell Research at Harvard University together with colleagues from the USA, Turkey and Puerto Rico, hypothesized that neurotization-mediated recovery is primarily attributable to CNS neuroplasticity that therefore manifests optimal response during particular therapeutic windows. To test this hypothesis in the rat, they anastomosed the T12 intercostal nerve to the ipsilateral L3 nerve root 1-4 weeks after T13-L1 midline hemisection. Neurobehavioral function, as assessed by locomotion, extensor postural thrust and sciatic functional index of SCI rats receiving neurotization 7-10 days postinjury, recovered to levels close to non-SCI controls with neurotization only, beginning 3-5 weeks postanastomosis. Conversely, hindlimb deficits were unchanged in hemisected controls with sham neurotization or 4 weeks-delayed neurotization, and in rats that had undergone T13-L1 transection plus bilateral anastomoses.

In addition to limited reinnervation in the target muscles, neurotized SCI animals demonstrated multiparameters of neural reorganization in the distal lumbar cord, including enhanced proliferation of endogenous neural stem cells, increased immunoreactivity of serotonin and synaptophysin, and neurite growth/sprouting, suggesting that anastomosing functional nerves with the nerve stump emerging distal to the hemisection may help re-establish locomotor pattern generation in the dysfunctional spinal cord. This conclusion was validated by the fact that severance of the T13-contralateral cord abolished the postanastomosis functional recovery.

While the goal of reclaiming neural control of a denervated organ via neurotization should be further explored, the authors suggest that this procedure could be utilized for the purpose of enhancing neuroplasticity and activating the inherent regenerative and repair potential of the spinal cord. This approach may have additional synergistic potential when combined with other treatment strategies that also aim at inducing neuroplasticity in the injured spinal cord. Task-specific physical activities (e.g., locomotor training), electrical stimulation and NSC transplantation, for example, may be employed in conjunction with the surgical procedure to provide additional augmentation of the plastic potential of the spinal cord and facilitate reorganization of neural circuitry to achieve greater functional and anatomical improvement.