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

Abstract

In the immediate management of patients with spinal cord injury (SCI), patients are typically observed for a period of time to determine whether voluntary control of bladder function returns. Therefore, bladder reinnervation surgeries are not likely to be performed immediately after the injury. We performed genitofemoral to pelvic nerve transfer (GF NT) surgery in canines at 1 and 3 months after bladder denervation (transection of S1 and S2 spinal roots) to determine whether this type of bladder reinnervation surgery has potential clinical feasibility. Nerve cuff electrodes were implanted on the genitofemoral nerves proximal to the pelvic nerve transfer site. Evidence for bladder reinnervation includes (1) increased bladder pressure and urethral fluid flow following electrical stimulation in four out of 20 nerve cuff electrodes implanted on the transferred GF nerves, (2) bilateral pelvic nerve stimulation induced bladder pressure and urethral fluid flow in three of four denervated animals with 1-month delay GF NT, and in five of six denervated animals with 3-month delay GF NT, and (3) abundant L1 and L2 spinal cord cell bodies (the origin of the GF nerve) retrogradely labeled with fluorogold injected into the bladder in all 10 of the GF NT animals, except one animal on one side. This study presents initial proof of concept that GF NT is a potentially viable clinical approach to reinnervation of the lower motor neuron-lesioned urinary bladder.

Neural reconstruction methods of restoring bladder function

“…Three weeks after injection of the fluorogold into the bladders for retrograde dye tracing, abundant retrograde transport of fluorogold to motor neurons in the upper lumbar cord was observed in three of four dogs with immediate transfer, and in all 10 animals that underwent delayed transfer, except unilaterally in one animal. Histochemical evidence of nerve regrowth across the repair site, 34, 35 and anterograde axonal tracing, further confirmed regrowth of axons from the transferred genitofemoral nerve into the bladder detrusor muscle, resulting in successful bladder reinnervation in the majority of animals in all groups.…”

“…19, 34, 35 In an initial study using intercostal nerves as donor nerves in one dog, 35 the immediate postoperative recovery was poor. We next examined the feasibility of transferring the ilioinguinal or iliohypogastric nerves, but each was too short to reach the bladder base.…”

“…Therefore, we decided to transfer the genitofemoral nerve, a mixed sensory and motor nerve, to the anterior vesical branch of the pelvic nerve (transected between the pelvic plexus and the bladder dome) in two intra-abdominal surgical conditions (Figure 6b): transection of the dorsal and ventral sacral roots within the spine followed by immediate transfer versus transection followed by a 1-month or 3-month delay before transfer. 34, 35 NCEs were implanted bilaterally in 2 of the 4 dogs with immediately GFNT and in all the dogs with 1month (n=4) and 3months (n=6) delay GFNT. At 32–138 days after surgery (mean 66 days), evidence of reinnervation included increased bladder pressure and urethral fluid flow after FES of the NCEs implanted on 2 of the 4 the immediately transferred nerves, and of four out of 20 NCEs implanted on the nerves that were transferred after a delay.…”

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).…”

Bladder Reinnervation: Is it Becoming a Reality?

“…The shamoperated animals had a significant number in the sacral cord region, the CG animals in the coccygeal cord segments, and the GF had a larger number in the lumbar cord. In a similar but larger study of 10 animals, 3 GF were able to generate a bladder pressure with electrical stimulation [12].…”