Spinal Cord Injury: Lessons from Locomotor Recovery and Axonal Regeneration in Lower Vertebrates

After severe spinal cord injury in adult higher vertebrates (birds and mammals), there normally is little or no axonal regeneration and virtually no recovery of voluntary locomotor function below the lesion. In contrast, certain lower vertebrates, including lamprey, fish, and some amphibians, exhibit robust axonal regeneration and substantial recovery of locomotor function after spinal cord injury. The remarkable behavioral recovery of lower vertebrates with spinal cord injuries is due to at least three factors: 1) minimal hemorrhagic necrosis at the injury site and the lack of a neurite growth–inhibiting astrocytic scar, 2) an environment in the spinal cord that is permissive for axonal regeneration, and 3) mechanisms for directed axonal elongation and selection of appropriate postsynaptic targets. The latter two features probably represent developmental mechanisms for axonal guidance and synaptogenesis that persist in the nervous systems of these animals well beyond the main phase of neural development. In the injured spinal cords of higher vertebrates, the full complement of manipulations necessary to promote functional regeneration and behavioral recovery is unknown. An understanding of the mechanisms that result in repair of spinal cord injuries in lower vertebrates may provide guidelines for identifying the requirements for functional spinal cord regeneration in higher vertebrates, including humans.