External Urethral Sphincter Activity during Micturition in the Adult Female Rat before and after Spinal Cord Injury
The Graduate School, Stony Brook University: Stony Brook, NY.
The process of micturition is fundamental to life and one of the major ways by which organisms excrete toxic byproducts of metabolism. To function efficiently, micturition requires reciprocal bladder contraction and urethral relaxation that is coordinated by the brainstem. Spinal cord injury (SCI) above the level of the lumbosacral spinal cord results in dysfunction of the lower urinary tract (LUT). One of the most common forms of LUT derangement is detrusor-sphincter dyssynergia (DSD), which is characterized by simultaneous contraction of the bladder and the external urethral sphincter (EUS) muscle due to the impairment of reflex and voluntary sphincter control. SCI patients suffering from this condition exhibit inefficient voiding and urine retention, and are prone to developing bladder and urinary tract infections. Proper bladder maintenance has a negative impact on the quality of life of the individual, thus dysfunction of the LUT following SCI is the subject of intense scientific research. One of the most prevalent animal models for studying micturition function is whole muscle EUS electromyographic (EMG) recordings during continuous flow cystometry (CM) in the adult female rat. The implementation of this animal model served as the basic experimental setup for the thesis research described in this document. This dissertation highlights three major research studies. (1) The first study established an in vivo model for studying the temporal patterns of EUS activity during micturition in the spinally intact rat using CM and EUS EMG recordings. Once the model was established and could be used to generate reproducible data, the aim of the study shifted to the identification and quantification of major changes in bladder and whole EUS muscle activity following chronic mid-thoracic spinal cord transection in the rat (1 - 8 weeks survival). (2) The second study successfully identified and categorized different EUS motor unit (MU) recruitment patterns during micturition. While this study also focused on quantifying EUS activity in the spinally intact and transected rat, it was done at the level of the single EUS MU in order to enhance our understanding of micturition in the rat before and after SCI. (3) The third and final part of this work concentrated on studying the role of γ-Aminobutyric acid-B (GABAb) receptor activation on micturition. Since baclofen, a GABAb agonist, has been shown to be effective in ameliorating LUT dysfunction and spasticity after SCI in humans and animals, intrathecal pharmacology was used to examine its effects on EUS activity in the spinally intact and transected rat. Together these three studies were designed to provide a more thorough understanding of micturition and SCI-induced LUT dysfunction in adult rat.