Recovery of bladder function worth the wait

One of the major clinical problems after complete SCI is the so-called neurogenic bladder. In this state, there is a lack of coordinated activity between the bladder and the external urethral sphincter which results in decreased voiding efficiency and increased pressure within the bladder. There is still relatively limited research into regenerative approaches to this important problem.

Yu-Shang Lee (#562.10) wanted to examine whether using a peripheral nerve graft to circumvent a transection injury (at the T8 level), in combination with chondroitinase and acidic fibroblast growth factor (aFGF) treatment would restore functional reflexes of the bladder. As before, the group implanted the ends of the nerve graft either side of the injury having first injected these sites with chondroitinase. The chondroitinase helps regenerating axons to both enter the graft and leave again at the other end. The fibroblast growth factor transformed astrocyte cells into a more elongated form – helping to support directional organised regeneration of axons. The group performed a number of treatment and control experiments and monitored bladder function over 6 months. All groups displayed bladder dysfunction initially. However, over the course of 6 months the full treatment group (nerve graft + chondroitinase + growth factor) began to show markedly improved function. At 6 months this treatment group had lower residual volume in the bladder after voiding, normalised bladder pressure and voiding intervals. Lower volumes and pressures would indicate less incontinence and distension - the latter being the most common trigger for autonomic dysreflexia.

The timeframe of recovery (many months) would suggest regeneration was involved. To test this hypothesis they recut the nerve graft and found the improved bladder function was abolished. Furthermore, tracing studies established that the regenerating axons had come from regions of brain normally associated with bladder control.