Modulation of Gonadotropin-Releasing Hormone Receptor Improves Voiding Hyperreflexia and Detrusor Sphincter Dyssynergia in Male Rats With Severe Spinal Cord Injury.

Abstract

Aims: The objective of the current study was to test the beneficial effects of a GnRH analog, leuprolide acetate (LA), over the urinary function in a rat model of lower urinary dysfunction by cystometry and electromyography in fully awake conditions in males with and without SCI.

Methods: Male Wistar rats that underwent spinal cord compression at T10 level were divided into three groups consisting of (1) SHAM, (2) SCI, and (3) SCI + LA 10 μg/kg i.m. (once a day for 3 days, then every 72 h until complete 13 doses). We then conducted awake cystometrograms and electromyograms of the external urethral sphincter (EUS) and compared urodynamic parameters between the three groups. The expression of Gonadotropin-releasing hormone receptor (GnRH-R) on the urinary bladder was evaluated and compared among three groups by real-time polymerase chain reaction (qPCR). Additionally, the hind limb movements related to micturition were analyzed.

Results: SCI induces detrusor sphincter dyssynergia, urinary malfunction, increased mRNA expression for the GnRH receptor in the urinary bladder in injured rats and increased hind limb movements related to micturition. Meanwhile, treatment with LA partially reverses these changes.

Conclusion: The potential of LA for the treatment of urinary disorders associated with SCI opens the way to a new therapeutic option for individuals with SCI who would like to have an impact on their daily lives.