Bypassing spinal cord injury: A novel therapy utilizing an intact peripheral nerve bridge.

摘要

We bypass spinal cord injury utilizing the T13 thoracic nerve to connect the brain to the caudal cord. We disconnected a thoracic spinal nerve (T13) from its muscle target. We then inserted the distal cut end of the nerve either into the intact spinal cord, to assess regeneration and synapse formation, or below a hemisection, to assess how well these regenerating axons restored function. We first discovered that motor axons in the T13 nerve could robustly regenerate into the spinal cord. Sensory fibers were unable to penetrate. To test for the presence of functional circuits we electrically stimulated the nerve and recorded postsynaptic responses in the cord and hind leg motor responses. Crushing the nerve bridge eliminated these potentials.;We then determined if the topographic regeneration and distribution of synaptic contacts on lumbosacral motoneurons varied as a function of time in uninjured animals. We examined the topography in animals between 2 weeks and 6 months. Animals at 2 weeks showed sparse undirected growth. Animals examined at 4 weeks had a majority of the regenerated axons present in the dorsal horn and intermediate zone, with paucity present in the ventral horn. Beyond 4 weeks, at time points from 2 to 6 months, the majority of the axons were in the ventral horn and motor nucleus. This suggests axon pruning. We then examined the synapses between regenerating motor axons and lumbar motoneurons. We first looked at the distribution of contacts and synapses made after more than four weeks of regeneration and found that they were present on or close to the cell body.;Finally, we examined animals that received a L2/3 hemisection. We found that axons grew directly to the ventral horn, indicating an extremely targeted regeneration pattern. The synaptic distribution was nearly identical to that in the uninjured animals. Behaviorally, we found that the T13 nerve reduced spasticity and triggered spontaneous movements.;These findings provide evidence that the T13 nerve bridge can create a new spinal circuit for the brain to adapt to and voluntarily control. This could finally provide the necessary neural infrastructure to bridge a spinal cord injury.