Establishing functional regeneration across the gap and down the rats' spinal cord presented challenges. The first obstacle was coaxing the regenerating axons to enter and transcend the bridge. Then the axons had to grow well beyond the bridge and form connections capable of relaying nerve signals once they arrived at their destination approximately two centimeters down the spinal cord.
To achieve these results, Silver and Lee added Fibroblast Growth Factor to help align the Schwann cells in the graft with the scar tissue cells at the bridge's interfaces. Next, they injected an enzyme called chondroitinase to break down inhibitory molecules that often form in scar tissue and curtail regeneration at both ends of the bridge.
"We were especially surprised and excited to discover that once a permissive environment was created, a subset of neurons situated largely within the brainstem, which play important roles in bladder function, slowly re-grew lengthy axons far down the cord," said Dr. Silver.
The model is highly relevant to people with a complete SCI, a total loss of function below the lesion, referred to as an A grade in the American Spinal Injury Association's impairment scale. The Cleveland-based team's work offers hope that the approach ultimately could translate to restoration of bodily functions for paralyzed humans.
"The future challenge will be to optimize the technique and further increase the intrinsic growth potential of these special neurons to facilitate more substantial and rapid axonal regeneration not only after acute but also after chro
|Contact: Jessica Studeny|
Case Western Reserve University