Evaluating potential therapies for bladder dysfunction in a mouse model of multiple sclerosis with high-resolution ultrasonography

Abstract

Background In multiple sclerosis (MS), demyelinating and neurodegenerative lesions develop throughout the central nervous system, which result in a loss of neurotransmission. As a result, people with MS exhibit a wide range of symptoms including dysfunction of the bladder, which can lead to urinary incontinence or retention. Such signs can develop in animal models of MS. Current assessments of bladder properties in animal models are generally invasive, electrophysiological techniques. Objective The use of a non-invasive, ultrasound system for measuring bladder volume in a mouse model of MS. Methods Chronic relapsing experimental autoimmune encephalomyelitis was induced in mice. The bladder volume was assessed using ultrasonography, during the disease course and following therapy with bethanechol chloride. Results It was demonstrated that volumes obtained ultrasonically positively-correlated (r = 0.960) with the urine volumes obtained by manual expression. It was also shown for the first time that bladder size increased significantly in mice with residual neurological deficit. Indeed, this increase in bladder size showed a strong, positive-correlation (r = 0.951) with the hind limb spasticity. Following treatment with bethanechol chloride, bladder volume significantly decreased in mice with chronic experimental autoimmune encephalomyelitis. Conclusion This study demonstrates a novel outcome measure in experimental MS that allows; repeated, non-invasive, high resolution ultrasonic monitoring of bladder function.