Bladder, Urethra and Anal Sphincter Reinnervation

描述(申请人提供)：对于脊髓损伤患者来说，恢复膀胱和肠道功能非常重要，对于截瘫患者来说，恢复膀胱和肠道功能甚至比恢复行走功能更重要。由于脊髓和膀胱之间的神经连接中断，导致软性膀胱麻痹的下运动神经元病变的患者不能使用功能性电刺激(FES)来诱导膀胱排空。这些患者需要新的神经通路来重新控制膀胱功能。这些研究的目的是为躯体神经移植重新支配膀胱的人体试验提供最终的证据。这项建议旨在实现以下特定目标：特定目标1：确定生殖股(GF)神经转移到骨盆神经前囊泡支是否对内括约肌和逼尿肌有神经支配。确定自主神经壁间神经节和平滑肌细胞是否都得到了功能上的重新支配。这些研究将验证这样一种假设，即从移位的GF神经经盆神经膀胱支进入膀胱的新神经可能一直延伸到尿路，重新支配内平滑肌括约肌和外骨骼肌括约肌。具体目标2：确定单侧膀胱神经移位术是否与双侧神经移位术一样，为膀胱排空提供了功能再支配。这种神经移位的临床应用将是单方面的，这一目的将检验这样的假设，即单侧神经移位为膀胱排空功能提供了足够的神经再支配。具体目的3：确定膀胱去神经后是否存在无FES的自发性膀胱排空。如果神经移位后膀胱自发排空功能恢复，则不需要植入FES系统。这一目的验证了这样一种假设，即在膀胱的GF神经再支配之后，中枢神经系统会发展出另一条诱导膀胱排空的途径。具体目标4：确定股前神经至阴部神经移位术是否也能恢复尿路和肛门括约肌的神经支配。控制尿便失禁可能需要新的通向尿路和肛门括约肌的神经通路。这一目标将检验这样一个假设，即阴部神经与股前神经的再支配将允许尿路和肛门括约肌的再神经支配，并恢复尿液和粪便的可控性。 公共卫生相关性：这项建议中描述的研究的目标是开发一种外科方法来重新支配受损的膀胱下运动神经元，从而使患者能够重新控制膀胱的排空。这些研究旨在为躯体神经移植重新支配膀胱的人体试验提供最终的证据。

DESCRIPTION (provided by applicant): In patients with spinal cord injury, regaining bladder and bowel function is of great importance, in paraplegics it is considered even more important than regaining walking function. Patents with lower motor neuron lesions resulting in flaccid bladder paralysis cannot use functional electrical stimulation (FES) to induce bladder emptying because the neural connection between the spinal cord and the bladder has been disrupted. These patients require new neural pathways to regain control of bladder function. The goal of these studies is to provide the final burden of proof for human trials of somatic nerve transfer to reinnervate the urinary bladder. This proposal is designed to achieve the following specific aims: Specific aim 1: Determine whether transfer of the genitofemoral (GF) nerve to the anterior vesicle branch of the pelvic nerve reinnervates the internal sphincter smooth muscle as well as the detrusor muscle. Determine whether both autonomic intramural ganglia and smooth muscle cells become functionally reinnervated. These investigations will test the hypothesis that the new nerves growing from the transferred GF nerve into the bladder through the vesical branch of the pelvic nerve may reach all the way down to the urethra to reinnervate the internal smooth muscle sphincter and external skeletal muscle sphincter. Specific aim 2: Determine whether unilateral GF to vesicle nerve transfer provides as much functional reinnervation for bladder emptying as the bilateral nerve transfer provides. Clinical application of this nerve transfer would be performed unilaterally and this aim will test the hypothesis that unilateral nerve transfer provides sufficient reinnervation for bladder emptying function. Specific aim 3: Determine whether spontaneous bladder emptying without FES occurs with GF nerve transfer to the vesical branch of the pelvic nerve following bladder denervation in the sacral spine. If spontaneous bladder emptying function does return after nerve transfer then implantation of the FES system would not be required. This aim tests the hypothesis that following GF nerve reinnervation of the bladder, the central nervous system develops alternate pathways that induce bladder emptying. Specific aim 4: Determine whether the urinary and anal sphincter muscles can also be reinnervated by anterior femoral to pudendal nerve transfer procedures. Control of urinary and fecal continence may require new neural pathways to the urinary and anal sphincters. This aim will test the hypothesis that reinnervation of the pudendal nerve with the anterior femoral nerve will allow both urethral and anal sphincter reinnervation and restore urinary and fecal continence. PUBLIC HEALTH RELEVANCE: The goal of the studies described in this proposal is to develop a surgical approach to reinnervate the lower motor neuron lesioned urinary bladder so the patient can regain control of bladder emptying. These studies are intended to provide the final burden of proof for human trials of somatic nerve transfer to reinnervate the urinary bladder.