Characterization of mouse neuro-urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation

Hiroki Ito, Marcus J. Drake, Christopher H. Fry, Anthony J. Kanai, Anthony E. Pickering*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
182 Downloads (Pure)

Abstract

Aim: To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in vivo-like neural connectivity. Methods: Adult male mice were decerebrated and arterially perfused with a carbogenated, Ringer's solution to establish the DAPM. To allow distinction between central and peripheral actions of interventions, experiments were conducted in both the DAPM and in a “pithed” DAPM which has no brainstem or spinal cord control. Results: Functional micturition cycles were observed in response to bladder filling. During each void, the bladder showed strong contractions and the external urethral sphincter (EUS) showed bursting activity. Both the frequency and amplitude of non-voiding contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the LUT resulting in retention in DAPM as it increased tonic EUS activity and basal bladder pressure in a dose-dependent manner (basal pressure increase also noted in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion blockade (hexamethonium), initially caused incomplete voiding, and both drugs eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed bladder distention-induced activity in the non-noxious range which was associated with pMM. Conclusions: This study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice.

Original languageEnglish
Pages (from-to)1302-1312
Number of pages11
JournalNeurourology and Urodynamics
Volume37
Issue number4
Early online date15 Jan 2018
DOIs
Publication statusPublished - 1 Apr 2018

Structured keywords

  • Anaesthesia Pain and Critical Care
  • Centre for Surgical Research

Keywords

  • external urethral sphincter
  • lower urinary tract
  • micturition
  • mouse
  • neural control

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