Bladder, Urethra and Anal Sphincter Reinnervation

膀胱、尿道和肛门括约肌神经再生

• 批准号: 10212464
• 负责人: Mary F Barbe
• 金额: $ 64.57万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10212464
• 关键词: Address; Animal Model; Animals; Anterior; Antibiotic Therapy; Bacteriuria; Behavior; Bladder; Blood Vessels; Canis familiaris; Cells; Chordoma; Clinical Trials; Decentralization; Development; Esthesia; Excision; Fiber; Funding; Future; Ganglia; Goals; Growth Factor; Horns; Housing; Human; Intervention; Intestines; Investigation; Laboratories; Lesion; Modeling; Motor; Motor Neurons; Muscle; Neonatal; Nerve; Nerve Transfer; Neural Pathways; Neurogenic Bladder; Operative Surgical Procedures; Organ; Patients; Pelvis; Peripheral; Peripheral Nerves; Posture; Pre-Clinical Model; Property; Quality of life; Recovery; Sex Functioning; Side; Smooth Muscle; Spinal; Time; Tissue Banks; Urethra; Urination; Urodynamics; Urothelial Cell; Urothelium; awake; cell type; clinical translation; effective therapy; improved; interstitial; nerve supply; obturator nerve; patient population; pre-clinical; preclinical study; recruit; reinnervation; restoration; sphincter ani muscle structure; success; tumor

Abstract: The animal studies in this renewal application will parallel the clinical trial studies to further understand the mechanisms of somatic reinnervation for restoration of bladder emptying function. Aim 1: Address the following questions: • Will administration of growth factors into the reinnervated urinary bladder wall improve recovery? • Which are the most effective growth factors to use? Will it be: a) Factors produced by the decentralized bladder cells (smooth muscle, intramural ganglia, interstitial, urothelial cells), b) Factors that promote neonatal survival of bladder spinal motoneurons; or, c) Factors that optimally attract the somatic motor fibers from the donor obturator nerve? • What growth factors promote functionally optimal afferent reinnervation? Aim 2: Address the following questions: • Is the one anterior vesical branch of the pelvic nerve on each side that is reinnervated by a portion of the obturator nerve branch sufficient to achieve effective bladder emptying and sensation? • Is the loss of innervation from transecting vesical branches alone enough to result in loss of bladder function or this there sufficiently retained innervation through other branches such that the voiding function recovers with time? • Is the recovery of voiding behavior truly the result of the new neural pathway from the nerve transfer or some other spontaneous recovery? • Will obturator to anterior branch of the pelvic nerve transfer performed before decentralization improve recovery of bladder function? Aim 3: Answer the following questions using the canine tissue bank accrued from the previous funding cycles and from the new animals in these proposed studies: • What properties have changed in the axotomized motor nerves and how are these altered by rerouting? • What types of efferent fibers are reinnervating the bladder from the obturator nerve and on what type of cells do these new fibers terminate? • Do the new bladder efferent fibers originate from the ventral horn, sympathetic chain ganglia or both? • What types of afferent fibers are growing into the bladder from the obturator nerve and what are their en- organ targets? Is it urothelium, intramural ganglia, muscles, or blood vessels?

抽象的： 本次更新申请中的动物研究将与临床试验研究并行，以进一步了解 体细胞神经支配恢复膀胱排空功能的机制。 目标 1：解决以下问题： • 将生长因子注入重新神经支配的膀胱壁会改善康复吗？ • 最有效的生长因子是： a) 由分散的膀胱细胞产生的因子（平滑肌、壁内神经节、间质、 尿路上皮细胞）， b) 促进膀胱脊髓运动神经元新生儿存活的因素；或者， c) 从供体闭孔神经最佳吸引体细胞运动纤维的因素？ • 哪些生长因子可促进功能最佳的传入神经再支配？ 目标 2：解决以下问题： • 是每侧骨盆神经的一个前膀胱分支，由神经的一部分重新支配。 闭孔神经分支是否足以实现有效的膀胱排空和感觉？ • 横切膀胱分支导致的神经支配丧失是否足以导致膀胱丧失 功能或通过其他分支充分保留神经支配，使得排尿功能 随着时间的推移会恢复吗？ • 排尿行为的恢复真的是神经转移或新神经通路的结果吗？ 其他一些自发恢复？ • 将闭孔器向盆腔神经前支转移前进行下放改善吗 膀胱功能恢复吗？ 目标 3：使用之前资助周期中积累的犬组织库回答以下问题 以及这些拟议研究中的新动物： • 轴突切除的运动神经的哪些特性发生了变化？这些特性如何通过重新布线而改变？ • 哪些类型的传出纤维从闭孔神经重新支配膀胱以及何种类型的传出纤维 这些新纤维会终止细胞吗？ • 新的膀胱传出纤维是否源自腹角、交感链神经节或两者？ • 哪些类型的传入纤维从闭孔神经长入膀胱，它们的作用是什么？ 目标器官是尿路上皮、壁内神经节、肌肉还是血管？