Functional reinnervation of the canine bladder after spinal root transection and genitofemoral nerve transfer at one and three months after denervation

Abstract

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.

FIG. 1

Functional electrical stimulation (FES): representative in vivo bladder pressure recordings during electrical stimulation. Stimulation of the implanted tripolar nerve cuff electrodes surrounding the genitofemoral nerve proximal to the nerve transfer site (left side) and intraoperative pelvic nerve stimulation with unipolar probe electrode immediately before the animals were euthanized (right side). Fluid flow out the urethra was noted during each electrical stimulation that induced increased bladder pressure. (Top) From dog 2 (Table 1) in which the genitofemoral nerve transfer (GF NT) surgery was performed 1 month after denervation. (Bottom) From dog 6 (Table 1) in which the GF NT surgery was performed 3 months after denervation.

FIG. 2

Neuronal cell bodies in the spinal cord retrogradely labeled with fluorogold injected into the urinary bladder. Representative micrographs from dog 2 (Table 1). Arrows indicate cells that were counted as positive for retrograde fluorogold labeling. Increased labeled cell bodies as well as increased number of labeled axons in the lumbar cord (top), compared to the sacral cord of the same animal (bottom). Scale bar = 50 μm.