Date on Master's Thesis/Doctoral Dissertation

8-2024

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Interdisciplinary Studies

Degree Program

Interdisciplinary Studies with a specialization in Translational Neuroscience, PhD

Committee Chair

Hubscher, Charles

Committee Co-Chair (if applicable)

Boakye, Maxwell

Committee Member

Boakye, Maxwell

Committee Member

El-Baz, Ayman

Committee Member

Howland, Dena

Committee Member

Ugiliweneza, Beatrice

Author's Keywords

spinal cord injury; epidural stimulation; sexual function; ejaculation; translational research; reproductive function; pre-clinical research

Abstract

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures rather than restoration of function. Unfortunately, SCI-induced urogenital dysfunction and its potential treatment are largely understudied even though regaining both urinary function and sexual function are a top priority among persons with SCI. In a rodent model of SCI, this work sought to determine the efficacy of spinal cord epidural stimulation (scES) as an intervention for urogenital dysfunction. First, three centers within the spinal cord (T13, L3 and L6) were targeted in female, Wistar rats with incomplete SCI to determine the impact stimulation has on urinary function during urethane-anesthetized ii cystometry. Then, the spinal generator for ejaculation was targeted in male, Wistar rats with anatomically complete and incomplete SCI to determine if scES could be used to induce ejaculation. Finally, an additional intervention, locomotor training, was added to determine if training could improve frequency of response to scES in rats with incomplete SCI. Measures of sperm health were also taken during the studies that focused on sexual health to document the timeline behind SCI-induced changes in spermatogenesis in a rodent model. scES was found to not only be impactful for triggering urine storage and bladder voiding behaviors when configured for urinary function, but was also found to induce ejaculation following SCI, highlighting the multifunctional effects of this treatment. This dissertation sets the frame-work for stimulation intensities, frequencies, and locations that are optimal for the recovery of urogenital function. These findings can be used to guide the translation of scES from bench to bedside.

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