Bladder Dysfunction in Sickle Cell Disease Is Associated with Inflammation and Oxidative Stress

Area of Science:

• Urology
• Hematology
• Pathophysiology

Background:

• Overactive bladder (OAB) is a growing concern in sickle cell disease (SCD) patients.
• The underlying mechanisms linking SCD to bladder dysfunction are not well understood.

Purpose of the Study:

• To investigate the roles of oxidative stress and inflammation in bladder dysfunction in a mouse model of SCD.
• To characterize bladder changes in the Townes transgenic SCD mouse model.

Main Methods:

• Cystometric analysis was performed on SCD mice and controls.
• In vitro detrusor contractility assays were conducted.
• Molecular analyses assessed markers of oxidative stress (NOX-2, 3-nitrotyrosine, MPO) and inflammation (IL-1β).

Main Results:

• SCD mice displayed an OAB phenotype with increased voiding frequency and reduced bladder compliance.
• Detrusor hypocontractility was observed in SCD mice, linked to reduced M3 receptor expression.
• Elevated markers of oxidative stress and inflammation were found in the bladders of SCD mice.

Conclusions:

• Oxidative stress, nitrosative stress, and inflammation contribute to bladder remodeling and dysfunction in SCD.
• The Townes SCD mouse model is valuable for studying lower urinary tract complications in SCD.
• Redox and inflammatory pathways represent potential therapeutic targets for bladder dysfunction in SCD.