Contractile and structural properties of detrusor from children with neurogenic lower urinary tract dysfunction.

Navroop Johal, Kevin Cao, Michael Millar, Reena Davda, Aamir Ahmed, Anthony J Kanai, Dan N Wood, Rita Jabr, Chris H Fry

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

Abstract

Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients urinary tract dysfunction remains, and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders - and any association with altered Wnt-signalling pathways that contribute both to foetal development and also connective tissue deposition. A comparator group was tissue from children with normally-functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components, except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. Whilst we cannot speculate about the reasons for these pathophysiological changes their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.
Original languageEnglish
JournalBiology
Publication statusAccepted/In press - 3 Sep 2021

Keywords

  • Bladder
  • paediatric
  • neuropathic bladder
  • detrusor smooth muscle
  • contraction
  • immunohistochemistry

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