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586: Early fesoterodine fumarate administration prevents the onset of neurogenic detrusor overactivity after spinalization in rats: Mechanism of action

Speaker
X. Biardeau, Montreal (CA)
Authors
Przydacz M. 1 , Loutochin G. 1 , Biardeau X. 1 , Cammisotto P. 1 , Zimoch J. 2 , Benlimame N. 3 , Campeau L. 1 , Corcos J. 1
Institutions
1Jewish General Hospital, Dept. of Urology, Montreal, Canada, 2University Children's Hospital, Dept. of Surgery, Zurich, Switzerland, 3Jewish General Hospital, Dept. of Cancer, Montreal, Canada, 4
Event
33rd Annual EAU Congress Copenhagen
Date – time - Location
18 March 2018, 14:00 - 15:30, Green Area, Room 1 (Level 0)
Session
Poster Session 43 - Whats new from the bench: Treating or preventing LUTS
Topic
Functional LUTS, incontinence and neuro-urology: Basic science

Introduction & Objectives

In spinal cord injury (SCI), onset of detrusor overactivity (DO) is detrimental for quality of life and renal function. Electrical neuromodulation implemented immediately after injury in patients after SCI is currently the only recognized way to prevent DO. As recently publish study analyzing urodynamics of spinal cord transected (SCT) rats has demonstrated that early administration of fesoterodine fumarate (FF) prevents the onset of DO [1], the aim of this experiment was to investigate whether the beneficial effect of FF was obtained by alternations in bladder muscarinic receptors.

Materials & Methods

33 Sprague-Dawley rats were allocated to 6 groups – Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered from post-op day 1. After 6 weeks, animals were sacrificed. Bladders were assessed by hematoxylin/eosin and Masson’s trichrome staining to analyze variations of bladders layers. Immunofluorescence staining against muscarinic receptors (M1 to M5) was performed to investigate distribution of the receptors. Prevalence of the receptors was analyzed by Western blots. Comparisons were conducted using Kruskall-Wallis test (post-hoc Dunn test).

Results

Morphological differences within bladder layers were not observed. Expression of M2 receptors was lower in all treated groups (Groups 3-6) when compared to SCT controls (Group 2) and statistical significance (p<0.05) was obtained in Groups 5 and 6 (Fig. 1). Expression of M3 receptors was higher in all treated groups (Groups 3-6) when compared to SCT controls (Group 2) and statistical significance (p<0.05) was obtained in Groups 4 and 5 (Fig. 1).
Image

Conclusions

Early FF administration in a SCT rat model modifies profile of bladder muscarinic receptors. The treatment effect is sustained after the wash-out period. This is probably how early administration of anticholinergics prevents the onset of DO after SCT.
1. Biardeau X, et al. Early fesoterodine fumarate administration prevents neurogenic detrusor overactivity in a spinal cord transected rat model. PLoS One. 2017 Jan 6;12 (1):e0169694.