# The Contribution of Central Nervous System Demyelination to Bladder Dysfuntion

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $451,000

## Abstract

Abstract
Myelination in the CNS is important for many higher order brain functions such as cognition, memory and complex
motor learning behaviors. Loss of CNS myelination in diseases like multiple sclerosis (MS) represents a critical
pathological event. Chronic demyelination is linked with disease progression making remyelination a therapeutic
target for addressing progressive MS. Loss of bladder control is a pervasive issue among multiple sclerosis (MS)
patients. It is also a leading cause of hospitalization among this patient population. It is estimated that nearly all MS
patients will experience lower urinary tract dysfunction. Since symptom prevalence increases with disease duration,
every MS patients will eventually experience urgency to urinate, urinary incontinence, frequency of urination, and/or
retention of urine. Urinary dysfunction in MS patients remain a difficult therapeutic challenge because the etiology of
bladder dysfunction among these patients is not well understood. While specific bladder dysfunction likely varies
from patient-to-patient and with age, sex and history of urinary tract infections, it is generally thought that
demyelination indirectly affects the bladder reflex and contributes to problems of urine storage (frequency) and
emptying (retention). However, our new data presented in this proposal support bladder dysfunction as a direct
corollary of CNS demyelination. Further, we hypothesize that CNS myelination may underlie the therapeutic efficacy
of antimuscarinic agents which are mainstay therapy for patients with neurogenic and non-neurogenic bladder
control disorders. Interestingly, an in parallel with the therapeutic effects of anti-muscarinic effects on remyelination
in human MS patients, these agents take several weeks to become maximally effective among even non-MS
patients with urinary disorders. Because anti-muscarinic agents have been implicated as a means to stimulate
oligodendrocyte maturation, and these agents can stimulate central nervous system (CNS) remyelination in MS
patients, we propose that CNS myelination underlies the development of bladder dysfunction. Therefore, bladder
function could therefore serve as a surrogate marker for evaluating the efficacy of CNS remyelinating therapies.
Hence, the objective of this study will be to determine whether CNS myelination underlies the therapeutic effects of
anti-muscarinic treatments on bladder function in a model of CNS demyelination. We hypothesize that CNS
demyelination is responsible for bladder dysfunction and the clinical benefits of muscarinic antagonists
that are clinically measured as enhanced control of bladder function, are mediated through remyelination
by oligodendrocytes. The results of this study will address several salient questions: (Aim 1) we will determine
whether CNS demyelination impairs bladder function, (Aim 2). we will establish whether oligodendrocytes are
required for the anti-muscarinic treatment effects on bladder dysfunction. ...

## Key facts

- **NIH application ID:** 10352892
- **Project number:** 1R21NS125332-01
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Stephen J Crocker
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2021-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352892

## Citation

> US National Institutes of Health, RePORTER application 10352892, The Contribution of Central Nervous System Demyelination to Bladder Dysfuntion (1R21NS125332-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10352892. Licensed CC0.

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