Lipid accumulation, macrophage activation, and liver dysfunction following spinal cord injury
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Date
2014-05
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The Ohio State University
Abstract
The spinal cord innervates all peripheral organs and, accordingly, spinal cord injury (SCI) has a chronic negative effect on peripheral organ function. As such, SCI patients have many chronic medical conditions that reduce health, life span, and quality of life. Metabolic syndrome is one such condition with high prevalence in the SCI population. The liver is essential for regulation of metabolism, and pathological changes in the liver contribute directly to developing metabolic syndrome. Surprisingly, the potential for SCI to disrupt liver functions has not been thoroughly examined. Therefore, we tested the hypothesis that SCI causes chronic liver pathology and dysfunction. Adult female rats were used as a model organism for spinal cord injury. Animals were perfused at different time points following SCI and tissue samples were collected for histological and molecular analyses. Adipose tissue showed changed expression of the adipokines resistin and adiponectin that modify inflammatory and metabolic function after injury. Significant lipid accumulation in the liver occurred by 1 day post injury (dpi) and remained elevated for at least 21 dpi compared to non-injured control animals. Detailed lipidomic analysis revealed that the increased lipid content is coupled with changes in the proportions of specific cytotoxic ceramide species. Coincident with the alterations in lipid content, inflammation increased acutely in the liver and remained elevated through 21 dpi. Inflammatory changes included hepatic macrophage activation from increased expression of interleukin inflammatory factors and TNF-α. Liver dysfunction is similar in rats receiving cervical or mid-thoracic SCI, suggesting these same effects likely occur in a large percentage of the SCI population. Given the liver’s essential role in metabolic function and the known metabolic problems after SCI, understanding the extent and cause of liver dysfunction following SCI may identify novel therapeutic targets for improving health, longevity, and quality of life for SCI patients.
Description
2014 Natural and Matematical Sciences Poster Forum Winner
2014 Denman Undergraduate Research Forum Honorable Mention
2013 Neuroscience Poster Day Winner
2014 Denman Undergraduate Research Forum Honorable Mention
2013 Neuroscience Poster Day Winner
Keywords
Spinal Cord Injury, Liver Dysfunction, Lipids, Inflammation, Ceramides, Adipokines