Characterization of Gastrointestinal Hormone Dysfunction and Metabolic Pathophysiology in Experimental Spinal Cord Injury
- 1 May 2023
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 40 (9-10), 981-998
- https://doi.org/10.1089/neu.2021.0490
Abstract
Cardiometabolic disease is a leading complication of spinal cord injury (SCI) that contributes to premature all-cause cardiovascular morbidity and early death. Despite widespread reports that cardioendocrine disorders are more prevalent in individuals with SCI than those without disability, a well-defined pathophysiology has not been established. Autonomic dysfunction accompanying disruption of autonomic spinal tracts may contribute to dysregulation of energy metabolism via uncoupling of integrated hunger and satiation signals. In governing human feeding behaviors, these signals are controlled by a network of enteroendocrine cells that line the gastrointestinal (GI) tract. These cells regulate GI peptide release and autonomic systems that maintain direct neuroendocrine communication between the GI tract and appetite circuitry of the hypothalamus and brain stem. Here we investigate gene-expression and physiological changes in GI peptides and hormones, as well as changes in physiological response to feeding, glucose and insulin challenge and evaluate GI tissue cytoarchitecture following experimental SCI. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kDyne) at T9, and a sham control group received laminectomy only. SCI results in chronic elevation of fasting plasma glucose levels, and an exaggerated glucose response after oral glucose and insulin tolerance test. Mice with SCI also exhibit significant alteration in gut hormone genes, plasma levels, physiological response to prandial challenge, and cell loss and gross tissue damage in the gut. These findings demonstrate that SCI has widespread effects on the GI system contributing to component Cardiometabolic disease risks factors and may inform future therapeutic and rehabilitation strategies in humans.Keywords
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