Nerve transfer for urinary bladder reinnervation: Organ donor and cadaver studies

用于膀胱神经支配的神经转移：器官捐献者和尸体研究

• 批准号: 10286172
• 负责人: Mary F Barbe
• 金额: $ 43.59万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286172
• 关键词: Anatomy; Animal Model; Animals; Anterior; Bilateral; Bladder; Bladder Control; Bladder Dysfunction; Brain Death; Cadaver; Canis familiaris; Catheterization; Cauda Equina Syndrome; Chordoma; Clinical; Clinical Trials; Competence; Decentralization; Development; Electric Stimulation; Ensure; Excision; Foreign Bodies; Foundations; Future; Heart; Human; Impairment; Injury; Intervention; Intestines; Laparotomy; Leg; Lesion; Methods; Modeling; Motor Cortex; Motor Neurons; Nerve; Nerve Fibers; Nerve Transfer; Neurons; Operative Surgical Procedures; Organ Donor; Outcome; Patient Care; Patients; Pelvis; Peripheral; Plant Roots; Population; Procedures; Protocols documentation; Recovery; Robotics; Sacral nerve; Sex Functioning; Skeletal Muscle; Sphincter; Spinal Cord; Spinal Dysraphism; Spinal nerve root structure; Surgeon; Techniques; Thigh structure; Time; Translations; Trauma; Urethra; Ventral Horn of the Spinal Cord; catheter associated UTI; clinical translation; conus medullaris; effective therapy; functional electrical stimulation; human subject; implantation; improved; motor neuron injury; obturator nerve; patient mobility; patient population; pre-clinical; pressure; recruit; reflex urine incontinence; reinnervation; restoration; sphincter ani muscle structure; spinal reflex; success; translation to humans; tumor

Aim 1: establish that functional electrical stimulation (FES) of specific anterior vesical branches of the pelvic nerve leading to the urinary bladder causes increased urinary bladder pressure in beating heart, brain dead human organ donors. Aim 2: develop a robotic-assisted laparoscopic approach for bladder reinnervation by nerve transfer of obturator nerve branches to anterior vesical branches of the pelvic nerve. This will form the foundation for a future clinical trial of nerve transfer surgery for restoration of bladder emptying function. Our ongoing preclinical canine studies over the past 18 years seek to develop surgical approaches to reinnervate the lower motor neuron-lesioned urinary bladder, urethra and anal sphincter. We had remarkable success and now plan to begin clinical translation. We clearly documented functional reinnervation of the bladder, assessed by induction of bladder contraction with electrical stimulation of transferred nerves when the reinnervation surgery is performed immediately after the decentralization,21 at one and three months20 and now at one year after decentralization.29 Because of this preclinical success, we propose clinical translation to human patients that have lost control of bladder emptying function. We have clearly demonstrated in cadavers that nerve transfer to the vesical branches of the pelvic nerve innervating to the urinary bladder is technically feasible using a variety of donor nerves.2,6,7 However, prior to drawing the conclusion that these methods will lead to functional detrusor reinnervation, we need to confirm that the anatomical configuration of these particular vesical branches of the pelvic nerve in humans is sufficiently similar to the animal model such that stimulation will result in effective detrusor contraction. This would provide the final evidence that the nerve transfer surgeries will be successful in human subjects. In contrast to the open laparoscopic approaches used in the animal model, establishing a robotic-assisted laparoscopic approach to obturator to pelvic nerve transfer for bladder reinnervation in non-embalmed cadavers will provide surgeons with expertise in the surgical procedures prior to a clinical trial and is expected, in comparison with the open procedure, to greatly reduce the recovery time and improve clinical outcomes. Long term impact: Successful confirmation in human cadavers and in beating heart organ donors will provide confidence that nerve transfer to these vesical branches of the pelvic nerve will reinnervate the detrusor and restore bladder emptying function to patients that have lost control of their bladder. There is no universally effective therapy for loss of detrusor activity, thus there is an urgent need to identify an effective treatment for this condition. The study described in this proposal will provide the final proof for the feasibility of reinnervation of the human urinary bladder for restoration of bladder emptying function and facilitate the development of adequate technical facility with this procedure to facilitate the translation of this to patients.

目的1：建立盆腔特定膀胱前支功能性电刺激（FES 导致膀胱的神经在心脏跳动时引起膀胱压力增加，脑死亡 人体器官捐献者目标2：开发一种机器人辅助的腹腔镜膀胱神经重建方法， 闭孔神经支移位至盆神经膀胱前支。这将形成 为今后神经移位手术恢复膀胱排空功能的临床试验奠定基础。 在过去的18年里，我们正在进行的临床前犬研究旨在开发手术方法， 使下运动神经元损伤的膀胱、尿道和肛门括约肌重新神经支配。我们有着非凡的 现在计划开始临床翻译。我们清楚地记录了 膀胱，通过电刺激转移的神经诱导膀胱收缩来评估， 在分散后立即进行神经再支配手术，21在一个月和三个月20，现在 29由于这种临床前的成功，我们建议将其临床转化为人类 膀胱排空功能丧失的患者。我们已经在尸体上清楚地证明了神经移植 应用各种供体，将膀胱神经的膀胱分支移植到盆神经的膀胱分支上， 然而，在得出这些方法将导致功能性逼尿肌神经再支配的结论之前，我们 需要确认这些特殊的骨盆神经膀胱分支的解剖结构， 人类与动物模型足够相似， 收缩。这将为神经移植手术在人类身上取得成功提供最终证据。 科目与动物模型中使用的开放式腹腔镜方法相比， 腹腔镜下闭孔肌盆神经移位膀胱神经重建术 在临床试验之前为外科医生提供外科手术方面的专业知识，与 开放手术，大大缩短了恢复时间，改善了临床结果。 长期影响：在人类尸体和跳动的心脏器官捐赠者中的成功确认将提供 神经转移到骨盆神经的这些膀胱分支将重新支配逼尿肌， 使膀胱失去控制的患者恢复膀胱排空功能。没有普遍 逼尿肌活性丧失的有效治疗，因此迫切需要确定有效的治疗方法 对于这种情况。本建议书中所述的研究将为以下可行性提供最终证据： 膀胱的神经再支配，以恢复膀胱排空功能，并促进 开发该程序的适当技术设施，以便于将其翻译给患者。