title: Coronavirus-induced demyelination of neural pathways triggers neurogenic bladder overactivity in a mouse model of multiple sclerosis.
abstract: In the present study, we aimed to determine whether mice with coronavirus-induced encephalomyelitis (CIE) develop neurogenic bladder dysfunction that is comparable with the neurogenic detrusor overactivity observed in patients with multiple sclerosis. Adult mice (C57BL/6J, 8 wk of age, n = 146) were inoculated with a neurotropic strain of mouse hepatitis virus (A59 strain) and followed for 4 wk. Inoculation with the virus caused a significant neural deficit in mice with an average clinical symptom score of 2.6 ± 0.5 at 2 wk. These changes were accompanied by 25 ± 5% weight loss at 1 and 2 wk postinoculation (P ≤ 0.001 vs. baseline) followed by a recovery phase. Histological analysis of spinal cord sections revealed multifocal sites of demyelinated lesions. Assessment of micturition patterns by filter paper assay determined an increase in the number of small and large urine spots in CIE mice starting from the second week after inoculation. Cystometric recordings in unrestrained awake animals confirmed neurogenic bladder overactivity at 4 wk postinoculation. One week after inoculation with the A59 strain of mouse hepatitis virus, mice became increasingly sensitive to von Frey filament testing with responses enhanced by 45% (n = 8, P ≤ 0.05 vs. baseline at 4 g); however, this initial increase in sensitivity was followed by gradual and significant diminution of abdominal sensitivity to mechanical stimulation by 4 wk postinoculation. Our results provide direct evidence showing that coronavirus-induced demyelination of the central nervous system causes the development of a neurogenic bladder that is comparable with neurogenic detrusor overactivity observed in patients with multiple sclerosis.
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Glenolden, Pennsylvania;
authors.forename: Matthew T
authors.initials: MT
authors.lastname: McMillan
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Glenolden, Pennsylvania;
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pan
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Glenolden, Pennsylvania;
authors.forename: Ariana L
authors.initials: AL
authors.lastname: Smith
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Glenolden, Pennsylvania;
authors.forename: Diane K
authors.initials: DK
authors.lastname: Newman
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ruggieri
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and Anna.Malykhina@uphs.upenn.edu.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Malykhina
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000473:pathology / Q000821:virology; D017934:Coronavirus; D018352:Coronavirus Infections / Q000150:complications* / Q000821:virology; D003711:Demyelinating Diseases / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000150:complications* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D006517:Murine hepatitis virus; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D010641:Phenotype; D010812:Physical Stimulation; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000503:physiopathology
keywords: animal model; multiple sclerosis; neurogenic bladder