Bladder, Urethra and Anal Sphincter Reinnervation

膀胱、尿道和肛门括约肌神经再生

• 批准号: 7879074
• 负责人: Mary F Barbe
• 金额: $ 32.81万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879074
• 关键词: Anterior; Ataxia; Bilateral; Bladder; Bladder Control; Bladder Dysfunction; Canis familiaris; Cauda Equina; Child; Clinical Trials; Contracts; Cutaneous; Denervation; Diffusion; Electric Stimulation; Ganglia; Goals; Human; Implanted Electrodes; Injury; Intestines; Investigation; Legal patent; Lesion; Modeling; Motor Neurons; Muscle; Myxoid cyst; Nerve; Nerve Transfer; Neural Pathways; Neuraxis; Operative Surgical Procedures; Paralysed; Paraplegia; Pathway interactions; Patients; Pediatric Hospitals; Pelvis; Pharmacology; Philadelphia; Plant Roots; Procedures; Quadriplegia; Skeletal Muscle; Smooth Muscle; Smooth Muscle Myocytes; Sphincter; Spinal Cord; Spinal cord injury; Surveys; System; Testing; Time; Urethra; Urethral sphincter; Vertebral column; Vesicle; Walking; clinical application; design; detrusor muscle; femoral nerve; implantation; in vivo; public health relevance; reinnervation; relating to nervous system; repaired; sphincter ani muscle structure; success; urinary

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.

描述（由申请人提供）：在脊髓损伤患者中，恢复膀胱和肠道功能是非常重要的，在截瘫患者中，它被认为比恢复行走功能更重要。由于脊髓和膀胱之间的神经连接已被破坏，导致弛缓性膀胱麻痹的患者不能使用功能性电刺激（FES）来诱导膀胱排空。这些病人需要新的神经通路来恢复对膀胱功能的控制。这些研究的目的是为躯体神经移植膀胱神经的人体试验提供最后的证据。本方案旨在达到以下具体目的：具体目的1：确定GF神经转移至盆腔神经前囊分支是否能支配内括约肌平滑肌和逼尿肌。确定自主神经节和平滑肌细胞是否都得到功能性的再神经支配。这些研究将验证一个假设，即从GF神经转移到膀胱的新神经通过盆腔神经的膀胱分支生长到尿道，并重新支配内部平滑肌括约肌和外部骨骼肌括约肌。具体目的2：确定单侧GF -囊泡神经移植是否能提供与双侧神经移植同样多的膀胱排空功能。该神经移植的临床应用将单侧进行，目的是验证单侧神经移植为膀胱排空功能提供足够的神经再支配的假设。具体目的3：确定骶棘膀胱去神经支配后GF神经转移至盆腔神经膀胱分支是否发生无FES的自发性膀胱排空。如果神经移植后膀胱排空功能恢复，则不需要植入FES系统。本研究的目的是验证在GF神经再支配膀胱后，中枢神经系统发展出诱导膀胱排空的替代通路的假设。具体目的4：确定尿和肛门括约肌是否也可以通过股前神经到阴部神经移植手术进行再神经支配。控制尿和大便失禁可能需要新的神经通路连接尿和肛门括约肌。这一目的将检验阴部神经与股前神经的再神经支配将允许尿道和肛门括约肌的再神经支配并恢复尿和大便失禁的假设。