Date on Master's Thesis/Doctoral Dissertation
Anatomical Sciences and Neurobiology
Anatomical Sciences and Neurobiology, MS
Committee Co-Chair (if applicable)
Spinal cord injury; kidney; neurotrauma
Spinal cord injury (SCI) results in neurological impairments including motor, sensory, and autonomic dysfunction. These neurological deficits result in a litany of complications apart from muscular paralysis, including bladder, bowel, cardiovascular, and sexual function. SCI-induced polyuria (the overproduction/passage of urine) remains understudied, and therefore mechanisms behind it are largely unknown and require extensive investigation for potential targeted therapies to improve quality of life. The objective of this dissertation was to investigate potential mechanisms of SCI-induced polyuria and explore potential therapies to improve quality of life in the SCI population. Metabolic cages, Western blot, enzyme-linked immunoassay, and immunostaining were first used to determine the timing of fluctuations in biomarkers associated with SCI-induced polyuria, including arginine vasopressin (AVP), atrial natriuretic peptide (ANP), vasopressin 2 receptor (V2R), natriuretic peptide receptor A (NPRA), and epithelial sodium channel (ENaC). Next, to identify which neural substrates induce polyuria with a T9-level SCI, a higher level (T3) contusion above the local sympathetic supply to the kidneys were also examined. Lastly, the effect of anantin (NPRA antagonist) on SCI-induced polyuria was explored, in addition to utilizing an established treadmill activity-based recovery training (ABRT) program. There were significant alterations of multiple biomarkers after SCI, beginning at 7 days post injury (dpi), in addition to a lower number of AVP-labeled neurons in the hypothalamus. By 7 dpi, continuing through 6 weeks post-SCI, T3 contused rats showed a significant increase in 24-hour void volume as well as significant changes in ANP and AVP like the T9 injury. There was also a significant decrease in AVP-labelled cells in the suprachiasmatic nucleus post-T9 and T3 contusion relative to controls. A reduction in void volume was found for rats having ABRT but not anantin treatment. A significant decrease in mean arterial pressure was measured in all animal groups lasting chronically, and there was a significant increase in serum potassium at 14 dpi in addition to a significant decrease in serum sodium at the chronic time point. Together, these studies provide a detailed account of systemic responses to SCI that are associated with SCI-induced polyuria and fluid homeostasis.
Gumbel, Jason H., "Investigations of potential mechanisms underlying spinal cord injury-induced polyuria." (2021). Electronic Theses and Dissertations. Paper 3739.