title: Spinal cord injury causes chronic liver pathology in rats.
abstract: Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI.
authors.affiliation: 1 Department of Neuroscience, The Ohio State University , Columbus, Ohio.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sauerbeck
authors.forename: J Lukas
authors.initials: JL
authors.lastname: Laws
authors.forename: Veera V R
authors.initials: VV
authors.lastname: Bandaru
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
authors.forename: Dana M
authors.initials: DM
authors.lastname: McTigue
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*
keywords: NASH; acute phase response; cytokines; metabolic syndrome