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)-1a, IL-1b, chemokine ligand-2, and tumor necrosis factor-a 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.

A Preliminary Cohort Study Assessing Routine Blood Analyte Levels and Neurological Outcome after Spinal Cord Injury

“…[30][31][32][33] In addition, a rat contusion model study found ALT to be significantly raised in the 21 days following injury, coupled with excess lipid accumulation and increased expression of pro-inflammatory genes. 34 Interestingly, this study also detected liver inflammation following lumbar SCI, 34 whereas previous studies in rats had shown that liver inflammation can occur within 30 min of SCI, 35 and that its severity correlates with level of injury. 31 AP, another analyte of the predictive ''liver function'' factor, is an enzyme that plays a significant role in bone mineralization, and has four isoenzymes, which are intestinal (IAP), placental (PLAP), germinal (GCAP), and tissue nonspecific (TNAP).…”

Gut dysbiosis impairs recovery after spinal cord injury

“…Compromised liver function may exacerbate the magnitude and effects of BT after SCI. Signs of liver disease (e.g., nonalcoholic steatohepatitis [NASH]) develop soon after SCI, and hepatic inflammation has been implicated as a key mediator of intraspinal inflammation (Campbell et al, 2008; Fleming et al, 2012; Anthony and Couch, 2014; Sauerbeck et al, 2015). Like the MLNs, the liver acts as a firewall, filtering gut microbes that drain from the intestine into the hepatic portal vein (Jenne and Kubes, 2013; Balmer et al, 2014).…”

Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats

“…To determine effect of TAM on tumorigenesis, the liver was extracted after fixation at 35 DPI. 29 Also, the brain was dissected, and both organs were dried overnight and weighed 24 h after dissection. 30 …”