Spinal Cord Injury Repair Research: A New Combination Treatment Strategy

Abstract

The optimism that a cure will soon be found for paraplegia and quadriplegia is strongly founded on the series of discoveries in the last two decades which showed that adult mammalian spinal cord axons can be made to regenerate given appropriate conditions and microenvironment. But then, why no cure yet in sight? Why is the delay? Spinal cord scientists are encountering a newfound obstacle in regeneration research. While axons do regenerate up and down through a graft/transplant placed at the injury site, they fail to regenerate further on once they reach healthy cord tissue beyond the injury zone. Research from our laboratory since the 1980s found that the principal reason for this failure of long distance regeneration is that the neural circuitry these axons have to traverse through are in a well-stabilized state which is unreceptive and refractory to new growth. Successful long distance regeneration is possible only within labilized (destabilized) neural tissues. We have shown simple and reliable methods of inducing labile state in adult spinal cord neural circuitry. This is achieved by inducing polyneuronal spinal motor control in the paralyzed limb muscles. We had predicted (Krishnan, 1991, 1983) two outcomes of inductive lability in paraplegia. One is partial revival of functions in the paralyzed limbs. The second outcome addresses effective relinking of the severed cord ends. Our preliminary results from adult paraplegic frogs convince us that inductive lability in these animals is capable of generating new growth and new connections in the distal isolated cord. Locomotor rhythm and function reappeared in the hind limbs, which enabled these animals to swim and progress on surface for long periods of observation up to 120 days. Based on these results we now recommend that inductive lability should be included as an essential component in the treatment strategy for spinal cord injury repair for effective relinking of the severed cord ends.

Key Words:

• Paraplegia
• Spinal cord repair
• Regeneration
• Labile state
• Polyneuronal control