Journal
EXPERIMENTAL NEUROLOGY
Volume 342, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2021.113725
Keywords
Fatty liver disease; Kupffer cells; TNF; Iron; TLR4; Hepatocyte ballooning; Obesity; ALT; Metabolic syndrome; White matter sparing
Categories
Funding
- National Institute of Neurological Disorders and Stroke (NINDS) [P30-NS045758, R01-NS082095]
- Craig H. Neilsen Foundation
- Belford Center for Spinal Cord Injury
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The study demonstrates that liver inflammation combined with spinal cord injury exacerbates intraspinal pathologies, including non-alcoholic steatohepatitis, and impairs locomotor recovery. Liver-derived protein Fetuin-A may act as a potential neuropathological mediator.
The current high obesity rates mean that neurological injuries are increasingly sustained on a background of systemic pathology, including liver inflammation, which likely has a negative impact on outcomes. Because obesity involves complex pathology, the effect of hepatic inflammation alone on neurological recovery is unknown. Thus, here we used a gain-of-function model to test if liver inflammation worsens outcome from spinal cord injury (SCI) in rats. Results show liver inflammation concomitant with SCI exacerbated intraspinal pathology and impaired locomotor recovery. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia and insulin resistance. Circulating and cerebrospinal levels of the liverderived protein Fetuin-A were higher in SCI rats with liver inflammation, and, when microinjected into intact spinal cords, Fetuin-A caused macrophage activation and neuron loss. Thus, liver inflammation functions as a disease modifying factor to impair recovery from SCI, and Fetuin-A is a potential neuropathological mediator. Since SCI alone induces acute liver inflammation, the liver may be a novel clinical target for improving recovery from SCI.
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