Stress and Traumatic Brain Injury Elicit Similar Cytokine Responses in Blood and Liver

Mildtraumatic brain injury (mTBI) is a major health issue comprising aheterogeneous and complex array of pathologies. Little is understood about the mechanisms of secondary injury in the evolution of damage after mTBI; however an apparent hepatic‐neural communication may generate a systemic inflammatory response (SIR). A stress‐mediated release of cortisol and catecholamines can enhance the SIR, leading to immunological dysfunction causing a retardation of healing in brain and systemic infrastructure. This study investigated the role of the SIR after TBI in male Wistar rats (N=129) that were subjected to one of four different procedures: mild TBI, moderate TBI, stress with mild TBI, or stress with sham TBI. Stress was generated using immobilization‐restraint tubes for 2 hours per day for the 4 days prior to injury. TBI was induced using a 500g weight‐dropmethod (from 100cm height for mild injury; and 120cm for moderate injury). Rats were sacrificed 6 hours, 48 hours, or 14 days after TBI or sham procedure. Serum corticosterone remained significantly elevated at 14‐days post‐injury. In order to correlate circulating inflammatory responses with liver specific responses, a panel of cytokines(e.g. IL6, TNFα, IFNγ, etc.) and SIR‐associated proteins (e.g. VEGF, TIMP, ICAM, etc.) were analyzed in liver tissue as well as in serum. Overall, we detected few differences in cytokine expression across the various experimental procedures or time‐pointsin serum or liver tissue (e.g. liver IFNγ at 48hr A.U.: modTBI 0.43±0.19;mildTBI 0.48±0.11; mildTBI w/stress 0.52±0.15; shamTBI w/stress 0.36±0.10; p=0.88). Thus, it appears that the SIR may not play a significant role in mild TBI pathology, specifically as it pertains to common circulating and hepatic cytokine pathways. Funded by USAMRMC. Author views not official US Army or DoDpolicy.