#1171

Using neurogenic bladder dysfunction rat model to evaluate the effect of brevetoxin on detrusor contractility

M. Chen¹, T. Hsu^1,2, Y. Fan^1,2, E. Huang^1,2

¹Taipei Veterans General Hospital, Department of urology, Taipei, Taiwan
²College of Medicine and Shu-Tien Urological Research Center, National Yang MingChiao Tung University, Department of urology, Taipei, Taiwan

Introduction:

Underactive bladder (UAB) is a voiding disorder characterized by impaired detrusor contractility, leading to lower urinary tract symptoms. UAB can result from age-related changes, iatrogenic injury, muscular dysfunction, or neurogenic disruption, with no currently effective treatments. Brevetoxin, a neurotoxin produced by Karenia brevis, which belongs to the group of polycyclic ether compounds and has a potent impact on the nervous system, affects neural transmission by modulating voltage-gated sodium channels (VGSCs). This study aimed to evaluate the therapeutic potential of brevetoxin in an animal model of detrusor underactivity.

Material and methods:

A neurological UAB rat model was established through pelvic nerve crush surgery. Brevetoxin (0, 1, 2, or 5 μg) was injected at four detrusor muscle sites and followed by cystometric evaluation was performed before and after treatment. After final assessment, bladders were harvested for histological and immunohistochemical analysis using H&E staining.

Results:

Pelvic nerve crush resulted in reduced micturition pressure (MP), increased micturition volume (MV), and prolonged micturition interval (MI). Following brevetoxin injection: (1) MP increased with higher brevetoxin doses; (2) MV increased at lower doses but declined at 5 μg; (3) MI followed a similar trend to MV. Immunohistochemical staining showed comparable bladder inflammation across all groups, indicating that brevetoxin\'s effects were not inflammation-mediated. Although some changes in bladder function did not reach statistical significance, the consistent trends in MV and MI indicate a potential therapeutic effect of brevetoxin, though the underlying mechanism remains unclear.