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Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction
Retnagowri Rajandram1, Teng Aik Ong2, Azad H A Razack2
1Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachuesetts; Department of Surgery, Faculty of Medicine, Kuala Lumpur, Malaysia; and.
American Journal of Physiology. Renal Physiology
|February 26, 2016
Summary
Ketamine abuse causes bladder dysfunction in mice, characterized by overactivity and increased voiding frequency. However, this study found no evidence of impaired bladder barrier function or structural changes in the urothelium.
Area of Science:
- Urology
- Pharmacology
- Toxicology
Background:
- Ketamine abuse is prevalent among young individuals.
- Ketamine abuse leads to lower urinary tract symptoms, but the exact cause is unclear.
- Impaired urothelial barrier function is a suspected cause of ketamine cystitis.
Purpose of the Study:
- To investigate the effect of ketamine on mouse bladder function.
- To determine if ketamine disrupts urothelial barrier function.
- To explore the mechanism of ketamine-induced cystitis.
Main Methods:
- Mice were administered ketamine for 12 weeks.
- Voiding behavior was assessed using spot assays.
- Bladder function was evaluated using cystometrograms.
- Urothelial permeability was measured with isotopic tracers in an Ussing chamber.
- Urothelial structure was examined using electron microscopy and immunofluorescence.
Main Results:
- Ketamine-treated mice exhibited increased voiding frequency and signs of bladder overactivity.
- No significant changes in urothelial permeability were observed.
- Urothelial structure, including umbrella cells and tight junctions, remained intact.
- Key barrier proteins like zonula occuldens-1 and uroplakin were normally distributed.
Conclusions:
- Ketamine administration induces voiding dysfunction in mice.
- Ketamine-induced cystitis in mice does not appear to be caused by disruption of the urothelial barrier function.
- The underlying mechanism of ketamine cystitis may involve factors other than urothelial barrier impairment.

