Bladder, Urethra and Anal Sphincter Reinnervation

膀胱、尿道和肛门括约肌神经再生

基本信息

批准号：
8459023
负责人：
Mary F Barbe
金额：
$ 39.3万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
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/8459023
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 Nerve Nerve Transfer Neural Pathways Neuraxis Operative Surgical Procedures Paralysed Paraplegia Pathway interactions Patients Pediatric Hospitals Pelvis Pharmacology Philadelphia Plant Roots Procedures 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

项目摘要

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.

描述（申请人提供）：对于脊髓损伤患者，恢复膀胱和肠道功能非常重要，对于截瘫患者来说，它被认为比恢复行走功能更重要。下运动神经元病变导致膀胱弛缓性麻痹的患者不能使用功能性电刺激（FES）来诱导膀胱排空，因为脊髓和膀胱之间的神经连接已被破坏。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体细胞神经移植重新支配膀胱的人体试验提供最终的证据。该提案旨在实现以下具体目标：具体目标1：确定生殖股（GF）神经转移至盆腔神经前囊支是否重新支配内括约肌平滑肌和逼尿肌。确定自主神经壁内神经节和平滑肌细胞是否在功能上重新受神经支配。这些研究将检验以下假设：从转移的 GF 神经通过骨盆神经膀胱分支生长到膀胱的新神经可能一直到达尿道，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 GF 至囊泡神经转移是否为膀胱排空提供与双侧神经转移一样多的功能性神经再支配。这种神经移植的临床应用将在单侧进行，这一目标将检验单侧神经移植为膀胱排空功能提供足够的神经支配的假设。具体目标 3：确定在骶棘膀胱去神经支配后，GF 神经转移到盆腔神经膀胱分支是否会发生无 FES 的自发膀胱排空。如果神经移植后膀胱自发排空功能确实恢复，则不需要植入 FES 系统。该目的检验了以下假设：在 GF 神经重新支配膀胱后，中枢神经系统会形成诱导膀胱排空的替代途径。具体目标 4：确定泌尿和肛门括约肌是否也可以通过股前神经至阴部神经转移手术重新神经支配。控制尿和大便失禁可能需要通往尿道和肛门括约肌的新神经通路。该目标将检验以下假设：阴部神经与股前神经的神经支配将允许尿道和肛门括约肌神经支配并恢复尿失禁。