Growth capacity ends when development is over During fetal development axons grow to their targets through tissues rich in laminin, other adhesion-promoting molecules and growth factors. Growing neurons actively synthesize proteins involved in assembly of the axonal cytoskeleton and membranes. At development’s end, expression of these extrinsic growth-promoting molecules and neuronal growth-related genes is decreased. When the spinal cord is injured, long axons are often severed or crushed, disrupting connections with the brain that relay sensory feedback and send motor commands to the limbs and body. If axons do not regenerate and re-establish lost neural circuits, these functions do not return (NINDS site).

   Many barriers inhibit axon regeneration After axonal injury or crush, formidable barriers obstruct growth cone migration and axon regeneration. Debris from the axon-ensheathing myelin contains proteins that inhibit growth cone motility. Astrocytes make a scar containing chondroitin sulfate proteoglycans that also block growth cone advance. These glia and other reactive cells release ephrins and semaphorins, the same negative cues that guide growth cones in embryos (YouTube video 5). Further, most injured neurons do not reactivate the genes that drive axonal growth, including cytoskeletal and membrane assembly.

   Extrinsic barriers can be reduced Animal studies of spinal cord injury have succeeded in diminishing or removing many inhibitors of axonal regeneration, the myelin proteins, chondroitin sulfate proteoglycans and repulsive molecules. These studies yielded some increased axonal regeneration, especially when several blockers were simultaneously targeted. Introduction of axonal growth factors stimulated additional improvements in axonal re-growth. Yet, even in the best cases, functional regeneration of damaged circuits was limited. Attention must also be paid to promoting the intrinsic growth capacities of injured neurons.

   Neuronal growth capacity must be increased Successful regeneration may require that neurons return to their embryonic growth state. Mechanisms are being designed to reprogram neurons to express genes that produce axonal growth and growth cone motility. Pharmacological and genetic strategies seek to activate regulatory pathways in neurons that stimulate axonal elongation and suppress metabolic activity that inhibits regeneration.

   The future for spinal cord regeneration is hopeful This progress, related research and bioengineering advances indicate that the potential for recovery from spinal cord injuries is greatly increased. Effective means are emerging to reduce the immediate pathological impact of spinal cord injuries. Multiple approaches are needed to reduce the inhibitory environment that develops after injury, while enhancing neuronal growth capacity. As occurs during development, regenerating axons may be guided by actively migrating growth cones. As an alternative to recreating former circuits, It may be possible to form new functional circuits with new neurons and/or new pathways. Finally, implantation of new materials and microdevices may promote neural regeneration and even take part in reestablishing sensory feedback and motor control between the brain and the spinal cord.