Functional Reinnervation of the Canine Bladder after Spinal Root Transection and Immediate End-on-End Repair

Abstract

The goal of this study was to transect and immediately repair ventral roots, selected by their ability to stimulate bladder contraction, to assess the feasibility of bladder reinnervation in a canine model. Brain-derived neurotrophic factor (BDNF) was delivered via an osmotic pump (0.5 or 5 mg/mL) to a cuff surrounding the reanastomosis site to the two root bundles on one side. Electrodes were implanted bilaterally immediately proximal to the site of surgical reanastomosis. Results were compared to four root-intact, control animals that also received bilateral electrode implantation. At 6-12 months post-surgery, five of eight nerve transected and repaired animals showed increased pressure and bladder emptying during electrical stimulation of the repaired ventral roots contralateral to the BDNF delivery side. Nerve tracing studies one year postoperatively determined the repaired roots to be S1 and S2 and showed regrowth of axons from the spinal cord to nerve sites proximal to the repair site and to the bladder, and the presence of neurofilament-labeled axons growing across the ventral root repair site. In conclusion, transected ventral and dorsal roots in the sacral spine can be repaired and are capable of functionally reinnervating the urinary bladder. This feasibility study paves the way for future studies utilizing other more proximal motor nerves to bypass the transection site for bladder reinnervation.

Functional Reinnervation of the Canine Bladder after Spinal Root Transection and Genitofemoral Nerve Transfer at One and Three Months after Denervation

“…Since we cut the S1 and S2 roots, any anomalous S3 innervation to the bladder would have been spared. In our pervious reports (Ruggieri et al, 2008;Ruggieri et al, 2006) and in this current report, only two nerve roots on each side of the spinal cord (S1 and S2) were found to induce bladder contractions during electrical stimulation in all dogs studied. However, it is possible that a very few number of motor fibers innervate the bladder in some animals through S3 roots; however, these were apparently below the level needed to induce bladder pressure increases during conus medullaris stimulation.…”

“…Using a canine model, we have previously shown that the urinary bladder can become reinnervated following sacral nerve root transection and immediate end-on-end repair based on increased bladder pressure upon FES and neurotracing studies using fluorescent and lipophilic dyes (Ruggieri et al, 2006). Similar nerve transection and immediate end-to-end suturing studies in pigs has demonstrated return of the micturition reflex in two animals at 14 and 20 weeks postoperatively (Conzen and Sollmann, 1982).…”

“…Bladder denervation was also performed as previously described (Ruggieri et al, 2006). Briefly, with the animal in the prone position, a 30-degree V-laminectomy of the L7 vertebral body and a partial laminectomy of the L6 and S1 vertebral bodies was done so that the S1 and S2 ventral roots innervating the bladder could be stimulated with a unipolar probe electrode.…”

“…Fluorogold retrograde neuronal tracing from the urinary bladder to the spinal cord was performed on all animals as previously described (Ruggieri et al, 2006;Ruggieri et al, 2008). Briefly, at 3 weeks before animals were euthanized, injections of 4% (w/v) fluorogold were made lateral to each ureteral orifice.…”

A Guidance Channel Seeded With Autologous Schwann Cells for Repair of Cauda Equina Injury in a Primate Model

“…Schwann cells derived from motor-specific axons (ie, ventral roots) appear to be better suited for sustaining motor axon elongation compared with those originating in the more traditional donor nerves (eg, sural) (82). In the dog, studies of bladder reinnervation after nerve root transection and repair using some of these newer strategies are promising (83,84). Finally, clinical trials of peripheral nerve repair with synthetic GC are under way, with encouraging results, provided that repair distances are short and resorbable GC are used (33).…”