Get access

S-Nitrosoglutathione protects the spinal bladder: Novel therapeutic approach to post-spinal cord injury bladder remodeling

Authors

  • Anandakumar Shunmugavel,

    1. Department of Pediatrics, Charles P. Darby Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina
    Search for more papers by this author
  • Mushfiquddin Khan,

    1. Department of Pediatrics, Charles P. Darby Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina
    Search for more papers by this author
  • Francis M. Hughes Jr.,

    1. Department of Urology, Charles P. Darby Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina
    Search for more papers by this author
  • J. Todd Purves,

    1. Department of Urology, Charles P. Darby Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina
    2. Department of Regenerative Medicine and Cell Biology, Pathology and Laboratory Medicine Service, Medical University of South Carolina, Charleston, South Carolina
    Search for more papers by this author
  • Avtar Singh,

    1. Ralph H. Johnson Veterans Administration Medical Center, Pathology and Laboratory Medicine Service, Medical University of South Carolina, Charleston, South Carolina
    Search for more papers by this author
  • Inderjit Singh

    Corresponding author
    1. Department of Pediatrics, Charles P. Darby Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina
    • Correspondence to: Inderjit Singh, Ph.D., 516, Darby Children's Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425. E-mail: saklaks@gmail.com

    Search for more papers by this author

  • Lori Birder led the peer-review process as the Associate Editor responsible for the paper.
  • Conflict of interest: none.

Abstract

Aims

Bladder and renal dysfunction are secondary events of the inflammatory processes induced by spinal cord injury (SCI). S-Nitrosoglutathione (GSNO), an endogenous nitrosylating agent is pleiotropic and has anti-inflammatory property. Hence, GSNO ameliorates inflammatory sequelae observed in bladder and renal tissues after SCI. Thus, we postulate that GSNO will improve the recovery of micturition dysfunction by quenching the bladder tissue inflammation associated with SCI.

Methods

Contusion-based mild SCI was induced in female Sprague–Dawley rats. Sham operated rats served as the controls. SCI rats were gavaged daily with GSNO (50 µg/kg) or vehicle. Bladder function was assessed by urodynamics at 2 and 14 days following SCI. Urine protein concentration and osmolality were measured. Bladder and kidney tissues were analyzed by histology and immunofluorescence for a variety of endpoints related to inflammation.

Results

Two days after SCI, urodynamics demonstrated a hyperreflexive bladder with overflow and no clear micturition events. By Day 14, vehicle animals regained a semblance of a voiding cycle but with no definite intercontraction intervals. GSNO-treated SCI-rats showed nearly normal cystometrograms. Vehicle-treated SCI rats had increased bladder wet weight, proteinuria, and urine osmolality at Day 14, which was reversed by GSNO treatment. In addition, the SCI-induced increase in immune cell infiltration, collagen deposition, iNOS, and ICAM-1 expression and apoptosis were attenuated by GSNO.

Conclusions

These results indicate that oral administration of GSNO hastens the recovery of bladder function after mild contusion-induced SCI through dampening the inflammation sequelae. These findings also suggest that GSNO-mediated redox modulation may be a novel therapeutic target for the treatment of mild SCI-induced renal and bladder dysfunction. Neurourol. Urodynam. 34:519–526, 2015. © 2014 Wiley Periodicals, Inc.

Ancillary