LAR inhibitory peptide promotes recovery of diaphragm function and multiple forms of respiratory neural circuit plasticity after cervical spinal cord injury

Following spinal cord injury (SCI), inhibitory molecules limit axon growth and recovery. This study tested a LAR inhibitory peptide in rats after cervical SCI, where neural circuitry becomes disconnected, causing diaphragm paralysis. LAR peptide was delivered at the injury site. At 8 weeks post-injury, the peptide significantly improved diaphragm function. It also promoted regeneration of axons and re-established connections. The study demonstrates that targeting LAR-based axon growth inhibition promotes respiratory neural circuit plasticity. This provides a new therapeutic strategy to improve respiratory consequences of SCI.

• 1
  LAR peptide significantly improved ipsilateral hemidiaphragm function, as assessed in vivo with electromyography recordings.
• 2
  LAR peptide promoted robust regeneration of ipsilateral-originating rVRG axons into and through the lesion site and into intact caudal spinal cord to reach PhMNs located at C3-C5 levels.
• 3
  LAR peptide stimulated robust sprouting of both modulatory serotonergic axons and contralateral-originating rVRG fibers within the PhMN pool ipsilateral/ caudal to the hemisection.