title: Neurotrophin therapy improves recovery of the neuromuscular continence mechanism following simulated birth injury in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Gill
authors.forename: Brian M
authors.initials: BM
authors.lastname: Balog
authors.forename: Charuspong
authors.initials: C
authors.lastname: Dissaranan
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Jiang
authors.forename: James B
authors.initials: JB
authors.lastname: Steward
authors.forename: Dan Li
authors.initials: DL
authors.lastname: Lin
authors.forename: Margot S
authors.initials: MS
authors.lastname: Damaser
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D036861:Delivery, Obstetric / Q000009:adverse effects*; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D009409:Nerve Crush; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D060525:Pudendal Nerve / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014621:Vagina / Q000293:injuries*
chemical_list: D019208:Brain-Derived Neurotrophic Factor