Dissertation
Elucidating spinal dopaminergic mechanisms that modulate the recovered micturition reflex after spinal cord injury
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2022
DOI:
https://doi.org/10.17918/00001234
Abstract
Traumatic spinal cord injury (SCI) often results in lower urinary tract (LUT) dysfunction. Although a spinal bladder reflex can be established over time, loss of supraspinal modulation causes detrusor-sphincter dyssynergia and bladder hyperreflexia, which manifests as incontinence and inefficient voiding. As a result of incomplete emptying, residual urine leads to urinary tract infections and, in some cases, kidney failure. Currently, urinary complications are one of the leading causes of morbidity and mortality in SCI patients. While spontaneous reorganization of spinal neuronal circuits occurs after injury, the extent is limited, and the underlying mechanisms are not well understood. Recently, we discovered a subpopulation of tyrosine hydroxylase (TH+) cells residing within the lower spinal cord and a low level of dopamine (DA) that persists in the lumbosacral cord which could modulate the recovered, though limited, bladder reflex. This data suggests that there are spinal endogenous dopaminergic mechanisms capable of regulating LUT function after SCI. These studies tested the hypothesis that spinal dopaminergic mechanisms, such as spinal TH⁺ cells and dopaminergic receptors, emerge as a compensatory response to help regulate micturition reflexes following SCI. Aim 1 examined the dopaminergic features and connectivity of spinal TH⁺ cells and how they are affected by injury. Aim 2 elucidated whether dopaminergic receptors regulate micturition reflexes and if pharmacological manipulation of such receptors can improve urinary performance after SCI. Overall, this work provides a significant contribution to the field by thoroughly investigating injury-induced molecular, anatomical, and functional alterations in the dopaminergic system and its effects on micturition reflexes subsequent to SCI.
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Details
- Title
- Elucidating spinal dopaminergic mechanisms that modulate the recovered micturition reflex after spinal cord injury
- Creators
- Jaclyn Helen DeFinis
- Contributors
- Shaoping Hou (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 158 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991018021331404721