Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Neurourol Urodyn. 2013 Jan;32(1):82-7. doi: 10.1002/nau.22264. Epub 2012 May 11.
Stress urinary incontinence (SUI) affects women both acutely and chronically after vaginal delivery. Current SUI treatments assume the neuromuscular continence mechanism, comprised of the pudendal nerve (PN) and external urethral sphincter (EUS), is either intact or irreparable. This study investigated the ability of neurotrophin therapy to facilitate recovery of the neuromuscular continence mechanism.
Virgin, Sprague Dawley rats received simulated childbirth injury or sham injury and treatment with continuous infusion of brain-derived neurotrophic factor (BDNF) or saline placebo to the site of PN injury. Continence was assessed by leak point pressure (LPP) and EUS electromyography (EMG) 14 and 21 days after injury. Structural recovery was assessed histologically. Molecular assessment of the muscular and neuroregenerative response was determined via measurement of EUS BDNF and PN β(II) -tubulin expression respectively, 4, 8, and 12 days after injury.
Following injury, LPP was significantly reduced with saline compared to either BDNF treatment or sham injury. Similarly, compared to sham injury, resting EUS EMG amplitude and firing rate, as well as amplitude during LPP were significantly reduced with saline but not BDNF treatment. Histology confirmed improved EUS recovery with BDNF treatment. EUS BDNF and PN β(II)-tubulin expression demonstrated that BDNF treatment improved the neurogenerative response and may facilitate sphincteric recovery.
Continuous targeted neurotrophin therapy accelerates continence recovery after simulated childbirth injury likely through stimulating neuroregeneration and facilitating EUS recovery and re-innervation. Neurotrophins or other therapies targeting neuromuscular regeneration may be useful for treating SUI related to failure of the neuromuscular continence mechanism.
压力性尿失禁（SUI）在阴道分娩后急性和慢性期都会影响女性。目前的 SUI 治疗方法假定盆底神经（PN）和尿道外括约肌（EUS）的神经肌肉控尿机制完整或不可修复。本研究探讨了神经营养因子治疗促进神经肌肉控尿机制恢复的能力。
处女、Sprague Dawley 大鼠接受模拟分娩损伤或假损伤，并接受持续输注脑源性神经营养因子（BDNF）或生理盐水安慰剂至 PN 损伤部位。损伤后 14 和 21 天，通过漏点压（LPP）和 EUS 肌电图（EMG）评估控尿能力。通过测量 EUS BDNF 和 PN β（II）-微管蛋白表达，分别在损伤后 4、8 和 12 天评估结构恢复情况。
损伤后，与 BDNF 治疗或假损伤相比，生理盐水组的 LPP 明显降低。同样，与假损伤相比，生理盐水组的 EUS 静息 EMG 幅度和放电率以及 LPP 期间的幅度均明显降低，但 BDNF 治疗组则没有。组织学证实 BDNF 治疗可改善 EUS 恢复。EUS BDNF 和 PN β（II）-微管蛋白表达表明 BDNF 治疗改善了神经发生反应，并可能促进括约肌恢复。
持续靶向神经营养因子治疗可能通过刺激神经再生和促进 EUS 恢复和再支配，加速模拟分娩损伤后的控尿恢复。针对神经肌肉再生的神经营养因子或其他治疗方法可能对治疗与神经肌肉控尿机制失败相关的 SUI 有用。
