Understanding the Underlying Mechanism of Age-Related Underactive Bladder and Proposing a Treatment Option to Mitigate its Symptoms

Authors

Arezoo Gerami Pour, Florida International UniversityFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Biomedical Engineering

First Advisor's Name

Zachary Danziger

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Jamie C. Theobald

Second Advisor's Committee Title

committee member

Third Advisor's Name

Ranu Jung

Third Advisor's Committee Title

committee member

Fourth Advisor's Name

Jessica Ramella-Roman

Fourth Advisor's Committee Title

committee member

Fifth Advisor's Name

Jacob McPherson

Fifth Advisor's Committee Title

committee member

Keywords

Underactive Bladder, Aging, Voiding Reflexes, Pudendal Neuropathy, Percutaneous Electrical Stimulation

Date of Defense

10-19-2021

Abstract

The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. UAB is characterized by inefficient voiding and bladder overdistension. Due to the unknown etiology, current therapeutic options are insufficient. Thus, a detailed understanding of its mechanism will facilitate the discovery of new treatments.

In Aim 1, we investigated the relationship between age and systems-level function of the LUT reflexes in three age groups of rats, testing the hypothesis that aging causes voiding reflexes to weaken. We systematically investigated the reflex bladder contractions evoked by combinations of rates of urethral infusion and bladder fill volumes as a function of age. We found that, with the same flow rate, older animals had fewer urethral to bladder contractions (augmenting reflex) than younger animals. Furthermore, old animals needed more fluid in their bladders before augmenting reflex (AR) could be triggered, suggesting a delay in switching the LUT to “voiding mode.”

In Aim 2, we recorded electroneurography from the sensory branch of the pudendal nerve (urethral afferents) in young and old rats to map how the interaction of age and urethral flow rate evokes discharges from sensory neurons. We found that both structural changes in the urethra and degradation of the urethral afferents are responsible for attenuated urethral afferent activation. This is critical because AR is mediated by urethral sensory nerves, and this reflex is required for efficient voiding.

Aim 3 examined the effects of percutaneous pudendal nerve stimulation on UAB symptoms in aged rats. The bladder was filled, and the stimulation was applied continuously until the end of the first voiding contraction. We showed that the minimally invasive stimulation of urethral nerves could increase voiding efficiency and prevent the bladder from overdistension.

In conclusion, we found that there is functional weakening in LUT reflexes with age and reduced urethral sensation, urethral muscle and nerve degradation might be contributing factors to that. This study helps us understand the underlying mechanism of age-related UAB, identify the mechanistic targets and develop therapies to mitigate its symptoms.

Identifier

FIDC010418

Previously Published In

1. Geramipour A and Danziger Z. C. Sensitivity of urethral flow-evoked voiding reflexes decline with age in the rat: insights into age-related underactive bladder. American Journal of Physiology-Renal Physiology 318 (6), F1430-F1440, 2020.

2. Geramipour A and Danziger Z. C., Age is associated with reduced urethral pressure and afferent activity in rat. Physiological Reports, 2021.

Recommended Citation

Gerami Pour, Arezoo, "Understanding the Underlying Mechanism of Age-Related Underactive Bladder and Proposing a Treatment Option to Mitigate its Symptoms" (2021). FIU Electronic Theses and Dissertations. 4898.
https://digitalcommons.fiu.edu/etd/4898