Bladder dysfunction in experimental autoimmune encephalomyelitis reflects clinical severity: A pilot study

  • Jamshid Faraji
    Corresponding authors at: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta T1K 3M4, Canada.
    Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
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  • Connor Gustafson
    Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
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  • Dennis Bettenson
    Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
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  • Hiromitsu Negoro
    Department of Urology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
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  • V. Wee Yong
    Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada
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  • Gerlinde A.S. Metz
    Corresponding authors at: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta T1K 3M4, Canada.
    Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada

    Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
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Published:September 29, 2022DOI:


      • Early life stress does not affect the severity of bladder dysfunction in EAE mice.
      • EAE severity is associated with an inflammatory response by GM-CSF cytokine.
      • Bladder dysfunction in terms of impaired micturition can be detectable in the EAE model.
      • EAE severity can be predicted by loss of bladder control in mice.
      • Progression of EAE can be reliably measured by VSOP.


      Multiple sclerosis (MS) is commonly associated with bladder dysfunction resulting in a progressive loss of voluntary control for urination over time. Here, we used the voided stain on paper (VSOP) method to investigate bladder function in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Using the VSOP test, we show that bladder dysfunction reflects pro-inflammatory processes of EAE and severity of clinical EAE symptoms, as characterized by increased urine voided volume per micturition (UVVM) on post-induction day 7 and decreased UVVM on post-induction day 14. The UVVM was closely related to a clinical disease index of EAE symptoms and plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine levels. UVVM was also sensitive to early life stress caused by animal transportation, which diminished UVVM at the peak of symptoms on post-induction day 14 in EAE mice. The results indicate that symptoms and progression of EAE can be reliably measured by VSOP as a non-motor function assessment.


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