J. Arzave1, K. Pool1, T. W. Costantini1, J. L. Weaver1 1University Of California – San Diego, San Diego, CA, USA
Introduction:
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients worldwide. Brain injury is associated with significant inflammation throughout the body. This inflammatory response in TBI leads to a secondary injury, worsening the effects of the original brain injury. The intestine is frequently cited as a source of inflammation in critical illness, but the mechanism of this response in TBI is unknown. The purpose of this study was to elucidate the inflammatory changes in the intestine after severe TBI in order to identify possible therapeutic targets.
Methods:
C57/B6 mice were given a severe TBI using a controlled cortical impact (CCI). Mice were anesthetized, had a craniotomy drilled in the skull, and a programmable impactor was used to drive a rod through the craniotomy directly into the brain. Sham animals were anesthetized but did not undergo craniotomy or CCI. Mice were sacrificed 4 hours after injury, and terminal ileum was collected and digested. Cytokines and chemokines were measured using the Proteome Profiler Array Mouse Cytokine Array Panel A (R&D Systems).
Results:
18 cytokines and chemokines were assessed in the intestine of sham and TBI mice. Two biological replicates were performed for each array, and two technical replicates for each cytokine within each array. IL-16 and ICAM-1 were highly-expressed in both sham and TBI mice. There was an increase in CCL5 (RANTES) expression in the TBI mice compared to sham (Figure 1).
Conclusion:
Expression of CCL5 was increased in the intestine after TBI. CCL5 is a driver of the intestinal inflammation seen in inflammatory bowel disease (IBD), and our findings suggest it contributes to the inflammatory response in TBI as well. Treatments targeting the CCL5 receptor have improved intestinal inflammation in models of IBD. Treatments designed to target CCL5 may reduce inflammation and improve outcomes in TBI patients.
