Acute inflammatory biomarker responses to diffuse traumatic brain injury in the rat monitored by a novel microdialysis technique

Neuroinflammation is a major contributor to the progressive brain injury process induced by traumatic brain injury (TBI), and may play an important role in the pathophysiology of axonal injury. The immediate neuroinflammatory cascade cannot be characterized in the human setting. Therefore, we used the midline fluid percussion injury model of diffuse TBI in rats and a novel microdialysis (MD) method providing stable diffusion-driven biomarker sampling. Immediately post-injury, bilateral amphiphilic tri-block polymer coated MD probes (100 kDa cut off membrane) were inserted and perfused with Dextran 500 kDa-supplemented artificial CSF to optimize protein capture. Six hourly samples were analyzed for 27 inflammatory biomarkers (9 chemokines, 13 cytokines and 5 growth factors) using a commercial multiplex biomarker kit. TBI (n=6) resulted in a significant increase compared to sham-injured controls (n=6) for 5 chemokines (Eotaxin/CCL11, Fractalkine/CX3CL1, LIX/CXCL5, MCP1α/CCL2, MIP1α /CCL3), 10 cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17α, IL-18, IFN-γ, TNF-α), and 4 growth factors (EGF, GM-CSF, Leptin, VEGF). Thus, diffuse TBI was associated with an increased level of 18 of the 27 inflammatory biomarkers at 1-6 time points during the observation period whereas the remaining 9 biomarkers were unaltered. The study shows that diffuse TBI induces an acute increase of a number of inflammatory biomarkers. The novel MD technique provides stable MD sampling suitable for further studies on the early neuroinflammatory cascade in TBI.