NT-3 Stimulates limited regeneration of the cortico-spinal tract following spinal contusion injury

A gradient of neurotrophic molecules stimulates regeneration in the adult spinal cord. Following spinal cord injury, axons are severed that never re-grow. Many of these axons have their cell body in the brain and extend their axon along distance down the spinal cord. Several factors appear to inhibit the regrowth of an axon across the injury site. These include the innate capacity of a neuron to grow a new axon, the presence of inhibitors that are naturally produced in the adult CNS, and the immune response to injury. Although several experimentalists have been able to get axons to initially re-grow using growth factors and artificial bridges, most of these procedures meet the same fate; lack of axonal growth through the injury site and to the original target. In these experiments we attempted to re-create an anatomical gradient of growth factors to stimulate directed growth of axons though the injury and on to their target. We found that using a combination of gene and cell-based gene therapy tools we were able increase growth of injured axons (e.g., regenerating axons in white above). Although this work is encouraging, we have a long way to go to stimulate substantial and functional regrowth.