Nerve transfer for restoration of lower motor neuron–lesioned bladder and urethra function: establishment of a canine model and interim pilot study results

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Previous patient surveys have shown that patients with spinal cord or cauda equina injuries prioritize recovery of bladder function. The authors sought to determine if nerve transfer after long-term decentralization restores bladder and sphincter function in canines.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Twenty-four female canines were included in this study. Transection of sacral roots and hypogastric nerves (S Dec) was performed in 6 animals, and 7 animals underwent this procedure with additional transection of the L7 dorsal roots (L7d+S Dec). Twelve months later, 3 L7d+S Dec animals underwent obturator-to-pelvic nerve and sciatic-to-pudendal nerve transfers (L7d+S Dec+Reinn). Eleven animals served as controls. Squat-and-void behaviors were tracked before and after decentralization, after reinnervation, and following awake bladder-filling procedures. Bladders were cystoscopically injected with Fluoro-Gold 3 weeks before euthanasia. Immediately before euthanasia, transferred nerves were stimulated to evaluate motor function. Dorsal root ganglia were assessed for retrogradely labeled neurons.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Transection of only sacral roots failed to reduce squat-and-void postures; L7 dorsal root transection was necessary for significant reduction. Three L7d+S Dec animals showing loss of squat-and-void postures post-decentralization were chosen for reinnervation and recovered these postures 4–6 months after reinnervation. Each showed obturator nerve stimulation–induced bladder contractions and sciatic nerve stimulation–induced anal sphincter contractions immediately prior to euthanasia. One showed sciatic nerve stimulation–induced external urethral sphincter contractions and voluntarily voided twice following nonanesthetized bladder filling. Reinnervation was confirmed by increased labeled cells in L2 and the L4–6 dorsal root ganglia (source of obturator nerve in canines) of L7d+S Dec+Reinn animals, compared with controls.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>New neuronal pathways created by nerve transfer can restore bladder sensation and motor function in lower motor neuron–lesioned canines even 12 months after decentralization.</jats:p></jats:sec>

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions

“…Post-decentralization delays of 1 or 3 months before similar transfer of genitofemoral nerves to anterior vesicle pelvic nerve branches, resulted in nerveevoked bladder contractions and urine flow in 3 of 4 dogs, and 4 of 6 dogs, respectively (70% when combined), when assessed at 7 months post-reinnervation (50). In a recent interim study (part 1 of this series), a post-decentralization delay of 12 months, then transfer of obturator nerves to anterior vesicle pelvic branches, resulted in nerve-evoked bladder contractions and urine flow in 2 of reinnervated dogs when assessed over 10 months post-reinnervation (60).…”

“…Axoguard nerve connectors (Axogen Corp, Alachua FL) were used to maintain transferred nerve coaptation and to reinforce the coaptation site that was covered in Tisseel fibrin sealant (Baxter, Deerfield, Il) For functional reinnervation of the external urethral and anal sphincters, a redundant branch of the sciatic nerve was transferred to branches of the pudendal nerve that induced urethral and anal sphincter contractions with intraoperative electrical stimulation. The effects of the pudendal nerve transfer on the urethral and anal sphincters are part of another study and are not presented in this manuscript, portions of which have been previously reported (60).…”

“…Current interventions for an atonic neurogenic bladder following a lower motor neuron lesion, 89 such as indwelling or intermittent catheterization (10), fail to target the source of the pathology and increase patient susceptibility to urinary tract infections (29). With the goal of targeting recovery of bladder function following a lower motor neuron injury, our group developed a model of surgical reinnervation via transfer of nerves that originate from other, higher spinal cord segments to either the anterior vesicle branch of the pelvic nerve to restore bladder contraction, or to the pudendal nerve to restore external urethral and anal sphincter contraction (6,13,14,25,48,49,51,52,60). In several studies, we used nerves originating from upper lumbar regions of the spinal cord, including obturator, femoral, and genitofemoral nerve branches, with success in reinnervation of the bladder immediately following, or 1, 3 or 12 months after sacral decentralization.…”

“…One of the reinnervated dogs even showed clear evidence of voluntary voiding during awake bladder filling, due to either a functional bladder contraction or a voluntary Valsalva maneuver (60).…”

Customized Neurotization for Hindlimb Hemiplegia After a Hemorrhagic Stroke

“…Currently, there are few data on neurotization for lower extremities hemiplegia after HICH,only several types of nerve transfer,such as L6-to-L6,L4-to-L5,and L3-to-L4 in animals,as well as obturator nerve to femoral nerve in humans,are reported for repairing the paralyzed lower-limb after central neurological diseases [25][26][27][28].Disappointingly, only weak and rough motions were observed in the proximal major joints(i.e.,hip and knee), without activities in the distal joints(i.e.,ankle).One of main reasons consists in inadequate option of a source nerve.Anatomically, ne motor activities are principally accredited to a synergy between exors and extensors chie y composed of antero-posterior muscle groups(quadriceps femoris,semimembranosus,gastrocnemius,and tib-ialis anterior,etc.) in the lower extremity.Simultaneously,those muscles,coincidentally from the L4 root, drive distal joints activities.In brief,L4 root mainly bifurcates to compose both femoral and sciatic nerves and is theoretically understood as an optimal donor nerve,but need to be quali ed experimentally in humans or rodents even if the initial role of the L4 could be undertaken by other lumbar roots following transection.…”