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Neurotrophin therapy improves recovery of the neuromuscular continence mechanism following simulated birth injury in rats

Authors

  • Bradley C. Gill,

    1. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio
    2. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio
    3. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
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  • Brian M. Balog,

    1. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
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  • Charuspong Dissaranan,

    1. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
    2. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
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  • Hai-Hong Jiang,

    1. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
    2. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
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  • James B. Steward,

    1. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
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  • Dan Li Lin,

    1. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
    2. Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
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  • Margot S. Damaser

    Corresponding author
    1. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio
    2. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio
    3. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio
    4. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
    5. Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio
    • Department of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Mail Stop ND20, Cleveland, OH 44195.
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  • Conflict of interest: none.

  • Lori Birder led the peer-review process as the Associate Editor responsible for the paper.

Abstract

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 βII-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 βII-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. Neurourol. Urodynam. 32: 82–87, 2013. © 2012 Wiley Periodicals, Inc.

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