Finding NeMO – Nerve-Sparing Midurethral Obstruction: a Pathophysiologically Accurate Model of Rodent Partial Bladder Outlet Obstruction

Abstract Objective To develop and evaluate a novel technique modeling partial bladder outlet obstruction (pBOO) using a Nerve-sparing Mid-urethral Obstruction (NeMO) approach. Materials and Methods Female unoperated rats were compared to rats after NeMO, NeMO-sham, proximal urethral obstruction (PU), or PU-sham. Residual volume, bladder capacity, voiding volume, and bladder mass were recorded; contractile characteristics of isolated bladder strips were also analyzed. Additionally, we quantitated nerve fibers at the bladder neck as well as extracellular matrix in the bladder wall. Results NeMO yields a more predictable degree of obstruction vs. PU, causes no animal mortality, and is easy to release. NeMO also results in a more moderate increase in bladder mass commensurate with human disease vs. the exaggerated response to PU, does not lead to the excessive bladder dilation observed after PU, while showing increased residual urine and fibrosis over time; thus closely modeling human pBOO pathophysiology. Importantly, PU-shams significantly incite both an undesirable mass-increase as well as bladder dysfunction, correlating with a denervation injury making them unsuitable as controls when modelling non-neurogenic pBOO. Bladder physiology and structure of NeMO-sham animals were indistinguishable from unoperated controls. The low complication rate and low variability of NeMO also can be applied to mice, opening the pBOO field to the full spectrum of transgenic manipulation. Conclusions NeMO is a pathophysiologically accurate modelling approach, with low variability and mortality, and newly paves the way for realistic and robust interpretation of omics and sequencing analytical methodologies. We therefore suggest it as new standard model when investigating pBOO.