Required growth facilitators propel axon regeneration across complete spinal cord injury

Adults cannot regrow transected axons across complete spinal cord injuries (SCI). The study identifies three mechanisms that are essential for developmental axon growth but are attenuated or lacking in adults. The researchers reactivated the growth capacity of mature descending propriospinal neurons and induced growth-supportive substrates. They also chemoattracted propriospinal axons to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents. The findings suggest that overcoming the failure of axon regrowth after maturity requires the combined sequential reinstatement of multiple developmentally essential axon-growth facilitating mechanisms. This identifies a mechanism-based biological repair strategy for complete SCI lesions.

• 1
  Combined delivery of AAV-OIC plus FGF+EGF+GDNF synergistically facilitated robust propriospinal axon regrowth in mice, passing through non-neural lesion cores and astrocyte scar borders, and penetrating well into spared grey matter.
• 2
  In rats, combined AAV-OIC plus two depots of FGF+EGF+GDNF exhibited robust propriospinal axon regrowth that routinely reached a full spinal segment or more past lesion centers and penetrated well into spared grey matter.
• 3
  Propriospinal axon regrowth was associated with a significant return of electrophysiological conduction across lesions, indicating functionality of the regrown axons.