Sophisticated models and methods for studying neurogenic bladder dysfunction

Abstract

To describe how the use of new and established animal models and methods can generate vital and far reaching experimental data in the study of mechanism underlying neurogenic bladder overactivity. Bladder and colonic irradiated mice and those with upper and lower motor neuron lesions were used to study neurogenic bladder overactivity. Methods included cystometry, tension measurements, afferent nerve recordings and optical mapping of action potentials and intracellular Ca(2+) transients. Recordings were made in a number of innovative preparations including in-line cultured cells, bladder-urethra sheets and cross-sections, spinal cord slices and the cerebral cortex. The animal models and methods used allow for the study of peripheral and central mechanisms of neurogenic overactivity. While colonic irradiation results in solely neurogenic dysfunction, spinal cord lesions also induce non-neural changes resulting in increased spontaneous detrusor contractions that can directly stimulate afferent nerves. Imaging of cultured bladder interstitial cells reveals spontaneous firing that could contribute to detrusor overactivity, while optical imaging of the spinal cord and brain could identify changes in central pathways that underlie lower urinary tract dysfunction. The animal models and methods described allow for the study of neurogenic overactivity at the peripheral, spinal and cortical levels. This may lead to greater understanding of sensory and motor mechanisms involved in incontinence, the contributions of interstitial cells and spontaneous detrusor contractions, and the involvement of the cortex.