Mature vertebral central nervous system neurons will not regenerate after injury. Although there has been a great deal of recent success in identifying the molecules that orchestrate the excitation and inhibition of damaged axons, significant axonal regeneration and functional recovery post spinal cord injury remains elusive. One explanation for this lack of success is that a single therapy regimen may not be sufficient to drive axonal regrowth and reorganization. Studies have shown that releasing the brakes of inhibition or depressing the accelerators of regeneration may be insufficient, in solo, to promote significant regeneration. In this proposal, a novel combinatorial therapeutic regimen will explore the synergistic effect of releasing inhibition while simultaneously accelerating regrowth and promoting neuroprotection to yield a marked degree of axonal regeneration in the rat spinal cord injury model. The anatomic results of the combinatorial treatment regimen will then be correlated with behavioral testing to assess the degree of functional improvement. ? ?
