Login to Access Video or Poster Abstract: MP85-05
Sources of Funding: This work was supported by P20 DK097819 grant (to A.M.P.), and AUA Scholar Award (to S.L.).

Introduction

Patients with multiple sclerosis (MS) develop a variety of lower urinary tract (LUT) symptoms. We recently characterized a murine model of coronavirus-induced encephalomyelitis (CIE model), and confirmed that CIE mice develop neurogenic bladder dysfunction that was comparable with neurogenic LUTS observed in MS patients. Identified mechanisms were morphological changes in the centers controlling micturition, spinal cord gliosis, and increased expression of pro-inflammatory cytokines. In the current study, we aimed to understand the long-term effects of neurodegenerative changes on micturition patterns and bladder physiology, as well as uncover the mechanisms of long-lasting neurogenic bladder dysfunction.

Methods

Adult C57BL/6J mice were inoculated with 20 µl of mouse hepatitis virus (MHV, N=44, CIE mice) or PBS (N=19). Neurological symptoms and mouse weight were recorded daily, and voiding behavior weekly up to 8 wks pi. Neurologic symptoms were evaluated by the Clinical Symptoms Score (CSS) on a scale from 0 (asymptomatic) to 4 (quadriparesis/paralysis). Detrusor contractility was evaluated in vitro at 10 wks. Based on CSS, CIE mice were assigned to 2 groups: recovery (REC group), and relapse (RELAP group). RELAP group was defined based on: (1) presence of symptom-free period at least for 24 hrs after initial rise in CSS, (2) presence of 2 symptom-free periods (24 h duration each), and (3) CSS>2 during the relapse.

Results

Long-term follow up of CIE mice revealed two different neurological phenotypes: 1-recovery from initial acute neurological impairment (REC, 73.5% of all CIE mice, N=25); and 2-relapse in symptoms (RELAP, 26.5% of all CIE mice, N=9). Eight percent of mice in REC group still had CSS≥2 at 8 wks in comparison to 22.2% in RELAP group. Animals in both REC and RELAP groups showed the most significant weight loss at 1wk. (22.3±0.28g at baseline vs 16.5±0.3g in REC group, and 9.2±0.86g in RELAP group, p<0.05). Isolated bladder strips from CIE mice did not have significant differences in muscarinic responses to EFS, however, RELAP group showed significantly decreased M3 responses along with increased micturition frequency at 5-6 wks.

Conclusions

Long-term follow up of CIE mice revealed two differential phenotypes of neurologic impairment mimicking two forms of MS in humans: relapsing-remissive MS and chronic inflammatory type of MS. Mice in RELAP group had a decreased response to M3 agonists suggesting that anti-muscarinic drugs may have limited effects on neurogenic bladder in this type of MS.

Funding

This work was supported by P20 DK097819 grant (to A.M.P.), and AUA Scholar Award (to S.L.).