Bladder, Urethra and Anal Sphincter Reinnervation

膀胱、尿道和肛门括约肌神经再生

• 批准号: 9988023
• 负责人: Mary F Barbe
• 金额: $ 8.6万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-02 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9988023
• 关键词: Animals; Anterior; Bilateral; Biological Assay; Bladder; Bladder Control; Canis familiaris; Decentralization; Electrodes; FPS-FES Oncogene; Goals; Human; Implant; Inferior hypogastric plexus structure; Lesion; Monitor; Motor; Motor Neurons; Nerve; Nerve Transfer; Operative Surgical Procedures; Paralysed; Patients; Pelvis; Plant Roots; Running; Sensory; Spinal Cord; Urethra; Urethral sphincter; Urodynamics; Vertebral column; femoral nerve; obturator nerve; pressure; radio frequency; reinnervation; sphincter ani muscle structure

Aim 1 - To determine whether reinnervation of the bladder by obturator nerve transfer and reinnervation of the urethral and anal sphincters by transfer of femoral nerve branches provides return of both continence and emptying function. We found that transfer of a primarily motor donor nerve (femoral nerve branches) provides superior bladder reinnervation than a mixed sensory and motor nerve (GFN).25 We also found that the pudendal nerve could be reinnervated by transfer of motor branches of the femoral nerve.15, 47 We have not yet reinnervated the bladder, urethra and anal sphincters in the same animal that would be important to human patients to restore voiding function, fecal and urinary continence. The obturator nerve, like the femoral nerve, is a primarily motor nerve, and its natural path runs very close to the pelvic plexus. Animals will be decentralized by bilateral transections of L7 and all roots caudal to L7 in the spinal column. The obturator nerve will be transferred bilaterally to the anterior vesical branch of the pelvic nerve (OBNT-to-PN) and branches of the femoral nerve will be transferred bilaterally to the pudendal nerve (FNT-to-PudN) as it emerges from the pudendal (Alcock's) canal. Un-anesthetized urodynamics will be performed monthly for 6 months; half receiving implanted radiofrequency (RF) micro-stimulators for FES of transferred obturator and femoral nerve branches to monitor return of nerve stimulation evoked detrusor, urethra and anal sphincter pressures, before the terminal assays at 6 months. Aim 2 - To determine whether the bladder, urethra and anal sphincters remain capable of being reinnervated after prolonged decentralization for up to one year. We found in a group of 5 dogs that 4.5±0.9 months after decentralization, stimulation of sacral roots or spinal cord segments does not increase detrusor pressure, proving decentralization. However, stimulating anterior vesical branches of the pelvic nerve (between the pelvic plexus and bladder dome) increases detrusor pressure in 5 of 5 decentralized animals.25 We also proved that the bladder can be reinnervated by genitofemoral nerve transfer (GFNT) at 1 and 3 months after decentralization.46 The longer after decentralization that the bladder remains capable of being reinnervated, the more feasible this approach would be for human patients with long standing flaccid bladder paralysis. Bladders will be decentralized, as described for aim 1. Cuff electrodes interfaced with RF micro-stimulators will be placed on anterior vesical branches of the pelvic nerve and on pudendal nerve branches as they emerge from the pudendal canal in a subset of these animals. The effects of nerve stimulation on detrusor, urethral and anal sphincter pressure will be determined at monthly intervals starting 3-4 weeks after decentralization and continuing to 6 or 12 months. OBNT-to-PN and FNT-to-PudN will be performed in separate groups of animals at 6 and 12 months after decentralization. These groups will be compared to sham-decentralized animals with identically implanted RF micro-stimulators.

目的1 -确定闭孔神经移位是否能重建膀胱神经， 通过转移股神经分支使尿道和肛门括约肌神经再支配提供了返回 同时具有清洗和排空功能。我们发现，转移主要运动供体神经（股神经 神经分支）提供了比感觉和运动神经混合（GFN）更好的上级膀胱神经再支配。 还发现阴部神经可以通过股神经运动分支的转移来重新神经支配。15， 47我们还没有在同一只动物的膀胱、尿道和肛门括约肌中进行神经再支配， 重要的是人类患者恢复排尿功能，粪便和尿液排泄。闭孔神经就像 股神经是主要的运动神经，并且其自然路径非常接近骨盆丛。动物 将通过双侧横断L7和脊柱中L7尾侧的所有根来分散。的 闭孔神经将被转移到双侧骨盆神经的前膀胱分支（OBNT到PN） 股神经的分支将被转移到双侧阴部神经（FNT到PudN），因为它 从阴部（Alcock's）管出来。将每月进行一次非麻醉尿动力学检查，持续6 月;一半接受植入式射频（RF）微刺激器，用于转移的闭孔FES， 股神经分支监测神经刺激诱发的逼尿肌、尿道和肛门括约肌的返回 压力，在6个月时终末试验前。目的2 -确定膀胱、尿道和 肛门括约肌在长时间的去中心化后仍然能够重新神经支配， 年我们发现，在一组5只狗，4.5±0.9个月后，分散，刺激骶神经根或 脊髓节段不增加逼尿肌压力，证明分散。然而，刺激 骨盆神经的膀胱前支（在骨盆丛和膀胱顶之间）增加逼尿肌 我们还证明，膀胱可以通过以下方式重新神经支配： 分散后1个月和3个月时的生殖股神经转移（GFNT）。 膀胱仍然能够被再神经支配，这种方法越可行， 对于长期存在的膀胱麻痹的病人来说。膀胱将是分散的，因为 描述目标1。将与射频微刺激器连接的袖带电极放置在膀胱前部 骨盆神经的分支和阴部神经分支，因为它们出现在阴部管在一个 这些动物的一部分。神经刺激对逼尿肌、尿道和肛门括约肌压力的影响将 从权力下放后3-4周开始，持续到6或12个月，每月测定一次。 在给药后6个月和12个月，将在不同的动物组中进行OBNT至PN和FNT至PudN试验。 分权将这些组与植入相同RF的假分散动物进行比较 微刺激器