The Role of Adenosine A1 Receptors in Regulating Inflammation after Experimental Traumatic Brain Injury in Mice: A Preliminary Report

Traumatic Brain Injury (TBI) induces adenosine accumulation as part of a putative endogenous neuroprotective response. TBI is associated with a marked inflammatory response and adenosine also has important effects on inflammation. Our hypothesis was that the A1AR plays a role in regulating inflammation after experimental TBI in mice. To test this hypothesis, we subjected A1AR ko mice and both wild type (wt) and heterozygote littermate controls (n=18 males) to experimental TBI using the controlled cortical impact (CCI) model and assessed markers of inflammation in brain tissue samples at 6 h using Luminex and ELISA. We focused on two cytokines, Interleukin‐6 (IL‐6) and Interleukin‐1α (IL‐1α), using ELISA. Brain tissue levels of IL‐1α were increased in the injured hemisphere of all groups after TBI vs naïve, however, the posttraumatic increase was attenuated in the ko after TBI. Brain tissue levels of IL‐6 were increased in the injured hemisphere of all groups after TBI vs naïve, while, the posttraumatic increase was attenuated in both the heterozygote and ko after TBI. Brain tissue levels of IL‐1α and IL‐6 were not increased after injury in the uninjured hemisphere and did not differ between genotypes. Our data suggest an attenuation of the increase in both IL‐1α and IL‐6 ‐ two established markers of inflammation ‐ in A1AR ko vs wild‐type mice after experimental TBI.