Muro-Neuro-Urodynamics; a Review of the Functional Assessment of Mouse Lower Urinary Tract Function

Abstract

Background: Mouse urodynamic tests are fundamental to understanding normal lower urinary tract (LUT) function. These experiments also contribute to our understanding of neurological dysfunction, pathophysiological processes, and potential mechanisms of therapy. Objectives: Systematic assessment of published evidence on urodynamics, advantages and limitations of different urodynamic measurements in mice, and consideration of potential implications for the clinical field. Methods: A search using specific search-terms for urodynamic studies and mice was conducted on PubMed (from inception to 1 July 2016). Results: We identified 55 studies examining or describing mouse neuro-urodynamics. We summarize reported features of mouse urodynamic function deriving from frequency-volume chart (FVC) measurements, voiding spot assays, filling cystometry, and pressure-flow studies. Similarly, an influence of the diurnal cycle on voiding is observed in mice and should be considered when interpreting rodent urodynamic studies, especially FVC measurements and voiding spot assays. Anaesthesia, restraint conditions, or filling rate influence mouse neuro-urodynamics. Mouse cystometric studies have observed intravesical pressure oscillations that accompany urine flow, attributed to high frequency opening and closing of the urethra. This characterization is not seen in other species, except rats. In contrast to human clinical urodynamics, the terminology of these examinations has not been standardized although many rodent urodynamic studies have been described. Conclusion: Mice have many anatomical and physiological similarities to humans and they are generally cost effective, and allow investigation of the effects of aging because of their short lifespan. There are some differences between mouse and human urodynamics. These must be considered when interpreting LUT function in mice, and translational value of murine disease models.

Keywords: cystometry; electromyography of the external urethral sphincter; frequency-volume chart; lower urinary tract dysfunction; mouse model.

Figure 1

A 24-h trace of a frequency-volume charts (FVC) (upper) and water intake (lower) of a male mouse at the age of 10 weeks. Each animal was separately placed in a conscious condition, without any restraint, in a metabolic cage that allows precise measurement of voiding episodes, voided volume, drinking episodes, and amounts (001–006 metMCM/TOA-UFabolic cage, Mitsubishi Chemical Medience, Tokyo, Japan). After 24-h adaptation, voided volume, voiding frequency, and water intake volume were recorded using a PowerLab® data acquisition system continuously for 24 h starting at 9:00 pm. The mice had free access to water and food during recording.

Figure 2

Cystometry and EMG recordings from spinal cord intact (A) and T8–T9 spinal cord injury (SCI; B) mice 2 weeks post-injury with the brain rostral to the supracollicular level sectioned from the brainstem and removed. Transperineal recording of the external urethral sphincter is combined with conventional filling cystometry. (A-1): This shows the guarding reflex that prevents leaking as bladder pressure approaches threshold. This is followed by increased phasic (bursting) and decreased tonic activity during which voiding occurs and pressure returns to baseline. (B): Following transection and the development of detrusor-sphincter-dyssynergia (DSD; B-1), when the bladder contracts, tonic sphincter activity increases resulting in non-voiding contractions and eventually overflow incontinence.