Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury.
BACKGROUND
Traumatic spinal cord injury (SCI) triggers a systemic inflammatory response (SIR) that contributes to a high incidence of secondary organ complications, particularly after a cervical or high-level thoracic injury. Because liver plays a key role in initiating and propagating the SIR, the aim of this study was to assess the effects that SCI at differing segmental levels has on the intensity of the inflammatory response in the liver.


METHODS
Using male Wistar rats, clip compression SCI was performed at the 4th thoracic (T4 SCI; high-level SCI) or the 12th thoracic (T12 SCI; low-level SCI) spinal cord segment. Sham-injured rats had a partial laminectomy, but no SCI. Leukocyte recruitment to the liver, hepatic blood flow, and hepatocellular injury/death were assessed using intravital microscopy and histology. Chemokine and cytokine concentrations were assessed in the liver. Outcomes were measured at 1.5 hours, 12 hours, and 24 hours after SCI.


RESULTS
At 12 hours after injury, T4 SCI caused a threefold increase in hepatic leukocyte recruitment compared with T12 SCI (p < 0.05). T4 SCI induced 50% more hepatocyte injury than T12 SCI at 12 hours (p < 0.05). Hepatic blood flow decreased after SCI, but not after sham injury, and stayed decreased only after T4 SCI at 24 hours after injury. The T4 SCI-induced changes were accompanied by increases in the hepatic concentrations of interleukin-1β, leptin, interleukin 10, and cytokine-induced neutrophil chemoattractant-1 at 1.5 hours.


CONCLUSIONS
Our findings indicate that traumatic SCI triggers an acute SIR that contributes to hepatocellular injury. SCI-induced remote injury/dysfunction to the liver appears to be transient and is more robust after an upper thoracic SCI compared with a lower thoracic SCI.
Division of Orthopaedics, Department of Surgery, University of Western Ontario, Victoria Hospital, London Health Sciences Center, London, ON, Canada. Jennifer.Fleming@lhsc.on.ca
Jennifer C
JC
Fleming
Christopher S
CS
Bailey
Hans
H
Hundt
Kevin R
KR
Gurr
Stewart I
SI
Bailey
Gediminas
G
Cepinskas
Abdel-Rahman
AR
Lawendy
Amit
A
Badhwar
D000818:Animals; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008102:Liver Circulation; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D018715:Microscopy, Video; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D013119:Spinal Cord Injuries / Q000150:complications*; D013904:Thoracic Vertebrae
D016207:Cytokines