Prolonged and intense neuroinflammation after severe traumatic brain injury assessed by cerebral microdialysis with 300 kDa membranes

Background: A neuroinflammatory response that may lead to edema and secondary brain damage is elicited in severe traumatic brain injury (TBI). Previous studies using microdialysis (MD) membranes with 100 k Dalton (kDa) cut-off found a transient intracerebral release of cytokines and chemokines without significant correlations to clinical course, intracranial pressure (ICP) or metabolites. In this study, a (300 kDa) MD probe was used to measure the levels of cytokines and chemokines in relation to ICP and metabolites. Methods: Seven patients with severe TBI received 2 MD catheters. In four patients sufficient dialysate could be retrieved for analysis from both catheters. MD samples were analyzed bedside, then frozen and analyzed for chemokines and cytokines using a multiplex assay (Mesoscale Discovery). Results: MD sampling was performed from 9 to 350 h. In total, 17 chemokines and cytokines were detected. Of these, IL-6, IL-8, IP-10, MCP-1 and MIP-1 beta were consistently elevated, and investigated further in relation to metabolites, and ICP. Levels of chemokines and cytokines were higher than previously reported from TBI pa-tients, and partially higher than those reported in patients with cytokine release syndrome. There were no significant differences between the two catheters regarding cytokine/chemokine concentrations, except for IL-6 which was higher in the peri-contusional area. No correlation with metabolites and ICP was observed. No significant increase or decline of chemokine or cytokine secretion was observed during the study period. Conclusion: Our data suggest that cytokine and chemokine levels reflect a perpetual, potent and pan-cerebebral inflammatory response that persists beyond 15 days following TBI.