title: Finding NeMO-Nerve-sparing Mid-urethral 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.
  
  
  METHODS
  Female unoperated rats were compared to rats after NeMO, NeMO sham, proximal urethral (PU) obstruction, or PU sham. Residual volume, bladder capacity, voiding volume, and bladder mass were recorded; the contractile characteristics of isolated bladder strips were also analyzed. Additionally, we quantitated nerve fibers at the bladder neck as well as the 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, and 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 modeling a non-neurogenic pBOO. The bladder physiology and structure of NeMO-sham animals were indistinguishable from those of 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 modeling 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 NeMO as a new standard model when investigating pBOO.
authors.affiliation: Division of Urology, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Sidler
authors.affiliation: Research Institute, Division of Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Aitken
authors.affiliation: Research Institute, Division of Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Jiang
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Dominika
authors.initials: D
authors.lastname: Bijos
authors.affiliation: Research Institute, Division of Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Neonatology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Jaques
authors.initials: J
authors.lastname: Belik
authors.affiliation: Division of Urology, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, and Department of Surgery, University of Toronto, Toronto, ON, Canada; Research Institute, Division of Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: darius.bagli@sickkids.ca.
authors.forename: Darius J
authors.initials: DJ
authors.lastname: Bägli
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D009119:Muscle Contraction; D051381:Rats; D014521:Urethra / Q000294:innervation* / Q000503:physiopathology / Q000601:surgery*; D001748:Urinary Bladder Neck Obstruction / Q000209:etiology*