Bladder, Urethra and Anal Sphincter Reinnervation

目的1-确定闭孔神经移位和闭孔神经再支配膀胱术 股神经分支移位重建尿道和肛门括约肌提供返流 既有控制功能，又有排空功能。我们发现，主要运动供体神经(股骨)的移位 神经分支)比感觉神经和运动神经(GFN)提供更好的膀胱神经再支配。 还发现阴部神经可以通过股神经运动支的移位来重新支配。 47我们还没有在同一动物身上重新支配膀胱、尿路和肛门括约肌 对人类患者恢复排尿功能、大小便控制很重要。闭孔神经，就像 股神经主要是运动神经，它的自然路径非常接近骨盆神经丛。动物 将通过双侧横断L7和脊柱中所有L7尾侧至L7的根来分散。这个 双侧闭孔神经移位至盆腔神经前膀胱支(OBNT-to-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(阿尔科克)运河冒出来。未麻醉的尿动力学检查将按月进行，为期6年 2个月；一半接受植入射频微刺激器，用于转移的闭孔器和 股神经分支监测神经刺激引起的逼尿肌、尿路和肛门括约肌的恢复 压力，在6个月的末梢化验前。目的2-确定膀胱、尿路和 肛门括约肌在长达一年的分散化后仍有能力重新支配 年。我们在一组5只狗身上发现，在去中心化、刺激骶神经根或 脊髓节段不会增加逼尿肌压力，这证明了权力的分散。然而，激动人心的 盆神经前膀胱支(盆丛和膀胱顶之间)增加逼尿肌 5个分散的动物中有5个有压力。25我们还证明了膀胱可以通过 去势后1个月和3个月行生殖股神经移位术(GFNT)。46术后时间更长 去中心化，即膀胱仍然能够被重新支配，这种方法就越可行 适用于长期患有软性膀胱麻痹的人类患者。膀胱将被下放，因为 目的1.将与射频微刺激器接口的袖套电极放置在膀胱前壁 盆神经的分支和阴部神经的分支在阴部管中长出 这些动物的子集。神经刺激对逼尿肌、尿路和肛门括约肌压力的影响 每个月确定一次，从权力下放后3-4周开始，持续到6个月或12个月。 OBNT-to-PN和FNT-to-PudN将在6个月和12个月后在不同的动物组中进行 分权。这些组将与植入相同射频的假分散动物进行比较 微刺激器。

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.