PMID- 22581583 OWN - NLM STAT- MEDLINE DCOM- 20130605 LR - 20240404 IS - 1520-6777 (Electronic) IS - 0733-2467 (Print) IS - 0733-2467 (Linking) VI - 32 IP - 1 DP - 2013 Jan TI - Neurotrophin therapy improves recovery of the neuromuscular continence mechanism following simulated birth injury in rats. PG - 82-7 LID - 10.1002/nau.22264 [doi] AB - AIMS: 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 beta(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 beta(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. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Gill, Bradley C AU - Gill BC AD - Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Balog, Brian M AU - Balog BM FAU - Dissaranan, Charuspong AU - Dissaranan C FAU - Jiang, Hai-Hong AU - Jiang HH FAU - Steward, James B AU - Steward JB FAU - Lin, Dan Li AU - Lin DL FAU - Damaser, Margot S AU - Damaser MS LA - eng GR - R01 HD038679/HD/NICHD NIH HHS/United States GR - R01 HD038679-11/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20120511 PL - United States TA - Neurourol Urodyn JT - Neurourology and urodynamics JID - 8303326 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology/*therapeutic use MH - Delivery, Obstetric/*adverse effects MH - Disease Models, Animal MH - Electromyography MH - Female MH - Nerve Crush MH - Peripheral Nerve Injuries/*drug therapy/etiology/physiopathology MH - Pudendal Nerve/injuries MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/drug effects/physiology MH - Treatment Outcome MH - Urinary Incontinence, Stress/*drug therapy/etiology/physiopathology MH - Vagina/*injuries PMC - PMC3419785 MID - NIHMS371372 EDAT- 2012/05/15 06:00 MHDA- 2013/06/06 06:00 PMCR- 2014/01/01 CRDT- 2012/05/15 06:00 PHST- 2011/12/16 00:00 [received] PHST- 2012/04/03 00:00 [accepted] PHST- 2012/05/15 06:00 [entrez] PHST- 2012/05/15 06:00 [pubmed] PHST- 2013/06/06 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - 10.1002/nau.22264 [doi] PST - ppublish SO - Neurourol Urodyn. 2013 Jan;32(1):82-7. doi: 10.1002/nau.22264. Epub 2012 May 11.