title: Rat animal model for preclinical testing of microparticle urethral bulking agents.
abstract: OBJECTIVE
  To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents.
  
  
  METHODS
  Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry.
  
  
  RESULTS
  Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent.
  
  
  CONCLUSIONS
  The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.
authors.affiliation: Department of Surgery, The University of Vermont, Burlington, VT.
authors.forename: Travis K
authors.initials: TK
authors.lastname: Mann-Gow
authors.forename: Jerry G
authors.initials: JG
authors.lastname: Blaivas
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: King
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Ghannam
authors.forename: Christine
authors.initials: C
authors.lastname: Knabe
authors.forename: Michael K
authors.initials: MK
authors.lastname: Lam
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kida
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Sikavi
authors.forename: Mark K
authors.initials: MK
authors.lastname: Plante
authors.forename: Jan
authors.initials: J
authors.lastname: Krhut
authors.forename: Peter
authors.initials: P
authors.lastname: Zvara
mesh_terms: D000537:Aluminum Oxide / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005549:Foreign-Body Reaction / Q000139:chemically induced / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010784:Photomicrography; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014521:Urethra / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D000537:Aluminum Oxide
keywords: animal model; ceramics; foreign-body reaction; urethral bulking; voiding function