1353 RECOVERY OF THE NEUROMUSCULAR CONTINENCE MECHANISM IS IMPROVED BY NEUROTROPHIN TREATMENT AFTER SIMULATED BIRTH INJURY IN RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence - Evaluation & Therapy III1 Apr 20121353 RECOVERY OF THE NEUROMUSCULAR CONTINENCE MECHANISM IS IMPROVED BY NEUROTROPHIN TREATMENT AFTER SIMULATED BIRTH INJURY IN RATS Bradley Gill, Charuspong Dissaranan, Hai-Hong Jiang, Brian Balog, Danli Lin, and Margot Damaser Bradley GillBradley Gill Cleveland, OH More articles by this author , Charuspong DissarananCharuspong Dissaranan Cleveland, OH More articles by this author , Hai-Hong JiangHai-Hong Jiang Cleveland, OH More articles by this author , Brian BalogBrian Balog Cleveland, OH More articles by this author , Danli LinDanli Lin Cleveland, OH More articles by this author , and Margot DamaserMargot Damaser Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1736AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Both acutely and long after childbirth, inadequacy of the neuromuscular continence mechanism comprised of the pudendal nerve (PN) and external urethral sphincter (EUS) has been implicated in Stress Urinary Incontinence (SUI) pathogenesis. Neurotrophins such as brain-derived neurotrophic factor (BDNF) are upregulated by innervated target organs after nerve injury to retrogradely stimulate neuroregeneration. However, concurrent EUS trauma from childbirth opposes the effects of PN injury on EUS BDNF upregulation. This study investigated functional and neuroregenerative responses of the neuromuscular continence mechanism to PN neurotrophin treatment after simulated childbirth injury. METHODS Age-matched virgin Sprague-Dawley rats underwent either untreated sham PN injury or simulated childbirth injury via PN crush and vaginal distention immediately treated with a 14-day infusion of either BDNF or saline placebo to the PN injury site. The neuromuscular continence mechanism was assessed 14 and 21 days after injury using leak point pressure (LPP) and EUS electromyography (EMG). The PN neuroregenerative response, indicated by cytoskeletal protein βII-tubulin expression, and EUS expression of BDNF were assessed by PCR 4, 8, and 12 days after injury with immunofluorescence utilized to confirm protein expression and EUS histology assessed as well. RESULTS LPP was significantly decreased with saline compared to BDNF treatment or sham injury 14 days after injury. Compared to sham injury, EUS EMG amplitude during LPP and at rest was reduced significantly with saline but not BDNF treatment 14 days after injury, as was resting EUS EMG firing rate. There were no significant EMG differences between groups 21 days after injury. EUS BDNF and PN βII-tubulin expression suggested BDNF improved the PN neurogenerative response and facilitated EUS recovery and re-innervation while saline did not. Compared to sham injury, histology revealed less atrophy and fibrosis in the EUS with BDNF than saline. CONCLUSIONS Continuous, targeted, neurotrophin therapy accelerated functional recovery of the neuromuscular continence mechanism after simulated childbirth injury. A combined stimulation of PN neuroregeneration and EUS recovery and re-innervation likely occurred. Neurotrophin treatment or targeted upregulation of neurotrophin expression may be useful for treating SUI in women. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e549 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bradley Gill Cleveland, OH More articles by this author Charuspong Dissaranan Cleveland, OH More articles by this author Hai-Hong Jiang Cleveland, OH More articles by this author Brian Balog Cleveland, OH More articles by this author Danli Lin Cleveland, OH More articles by this author Margot Damaser Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...