Functional and molecular characterisation of the bilateral pelvic nerve crush injury rat model for neurogenic detrusor underactivity

• Published in: BJU international Vol. 123; no. 5A; pp. E86 - E96
• Main Authors: Dewulf, Karel, Weyne, Emmanuel, Gevaert, Thomas, Deruyver, Yves, Voets, Thomas, Ridder, Dirk De, Everaerts, Wouter, Albersen, Maarten
• Format: Journal Article
• Language: English
• Published: England 01-05-2019
• Subjects: Animals; Crush Injuries - complications; denervation; detrusor underactivity; Disease Models, Animal; Hypogastric Plexus - injuries; Male; pelvic nerve; Peripheral Nerve Injuries - complications; rat model; Rats; Rats, Sprague-Dawley; smooth muscle; underactive bladder; Urinary Bladder, Underactive - etiology; Urinary Bladder, Underactive - physiopathology; detrusor underactivity; smooth muscle; rat model; denervation; pelvic nerve; underactive bladder
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/bju.14649

Objectives
To create a rat model for neurogenic detrusor underactivity (DU) by bilateral pelvic nerve crush injury (BPNI) and to study temporal changes in detrusor contractility and morphology.
Materials and Methods
Male Sprague‐Dawley rats were subjected to BPNI or sham surgery and evaluated at 1, 3 and 9 weeks after surgery. Bladder function was determined in vivo by awake cystometry, micturition pattern analysis, and 24‐h urine collection. Bladders were harvested for in vitro pharmacological investigation by isometric tension recording. Bladders and major pelvic ganglia were investigated by quantitative reverse transcription‐polymerase chain reaction and histochemistry.
Results
Overflow incontinence was observed at 1 week after BPNI. At 3 and 9 weeks after BPNI, rats showed a bladder phenotype characteristic for DU with increased post‐void residual urine volumes, reduced voiding efficiencies, and lower maximum pressures. In isolated bladder strips, contractile responses to KCl, carbachol, and α,β‐methylene adenosine 5′‐triphosphate (α,β‐mATP) were preserved. On the other hand, neural‐induced contractility was reduced after BPNI, in line with reduced expression of protein gene product 9.5 and choline acetyltransferase in the major pelvic ganglion at 1 week after BPNI. The bladder‐to‐body weight ratio and detrusor thickness increased after BPNI, indicating detrusor hypertrophy to compensate for the reduced neural input.
Conclusions
BPNI induces a rat model for neurogenic DU. In this model, the detrusor maintains its contractility but denervation of the detrusor was observed.