Central mechanisms of experimental Tbi-induced gastroparesis
Open Access
- Author:
- Pugh, Kristina Renee
- Graduate Program:
- Anatomy
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- March 26, 2014
- Committee Members:
- Gregory Michael Holmes, Thesis Advisor/Co-Advisor
Dr Patricia Mc Laughlin, Thesis Advisor/Co-Advisor
R Alberto Travagli, Thesis Advisor/Co-Advisor - Keywords:
- Traumatic brain injury
gastric motility
gastric emptying
corticotropin releasing factor - Abstract:
- Traumatic Brain Injury (TBI) in humans occurs as a result of acceleration and/or deceleration forces, blunt force impact, and penetrating wounds to the head. Individuals with TBI often present with a poor response to supplemental nutritional support while in intensive care and the mechanisms for this failure remain unknown. Our own preliminary data show that experimental TBI induces gastrointestinal (GI) dysmotility while other experimental models have demonstrated that TBI initiates a cascade of GI mucosal barrier pathologies, all of which are hypothesized to contribute to prolonged dysregulation of nutrient homeostasis. The control of gastric motility is dominated by vagal neurocircuitry and the vagal connection between higher brain regions and the GI tract, referred to as the brain-gut axis, is an important link in the modulation of GI function by homeostatic and emotional processes. It has been shown that TBI induces at least a brief upregulation of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) of the hypothalamus and the amygdala. Experimental models of stress-mediated gastric dysmotility have demonstrated the role of CRF in GI dysfunction. The central hypothesis of this thesis is that post-TBI upregulation of CRF plays a key role in the central mechanisms leading to post-TBI gastroparesis. In all experiments, male Wistar rats were used and injured via the fluid percussion model (FP-TBI). Outcomes were measured using a combination of immunohistochemical, molecular, physiological and non-invasive gastric emptying tests. Parameters of lesion severity were determined by peak pressure of the fluid percussion wave, righting time, and mortality rate. Analysis of these parameters revealed that experimental subjects segregated into three basic populations, mild-injury, moderate-injury and fatal-injury. In control rats, t(max) and t1/2 measurements of gastric emptying were not significantly different from FP-TBI at any post-surgical time point. There was a non-significant trend for an elevation of maximum cumulative dose at one week post injury (P=0.08). Immunohistochemical detection of CRF could not reliably be detected by the immunohistochemical protocol employed in this study. Microdissection of the PVN from control and FP-TBI rats yielded no significant differences in CRF mRNA expression between groups (P>0.05). Additionally, microinjection of oxytocin into the DVC of control, mild and moderate FP-TBI rats did not significantly alter gastric tone, although there was a non-significant trend toward a reversal of the effect of oxytocin in moderate FP-TBI. It was concluded from these present data that CRF is not robustly upregulated following the current FP-TBI parameters. The post-TBI mechanism leading to gastric dysfunction remains to be determined by further experimentation.