A dynamic and complex early inflammatory response in blood and cerebrospinal fluid of severe traumatic brain injury patients: A dual platform analysis

Introduction: Severe traumatic brain injury (TBI) is associated with high mortality and long-term disability. Inflammation plays a central role in TBI pathophysiology, yet the early dynamics of inflammatory mediators in blood and cerebrospinal fluid (CSF) remain incompletely understood. Moreover, analytical methods differ across studies and have rarely been directly compared. Aim To characterize the inflammatory response in blood and CSF during the first week after severe TBI and to assess correlation between electrochemiluminescence (ECL) and proximity extension assay (PEA). Methods A prospective observational study was conducted recruiting adult severe TBI patients (n = 21) requiring neurocritical care. Plasma and CSF samples were collected at two time points: days 1–3 and days 4–8. Orthopedic patients with minor extremity fractures (n = 11) served as controls. Inflammatory mediator levels were quantified using ECL (11 mediators) and PEA (45 mediators). Group differences, temporal changes, and inter-platform correlations were analyzed. Results Both plasma and CSF from TBI patients displayed a pronounced inflammatory response, with multiple mediators significantly altered compared to controls. In plasma, 16 mediators were increased and 5 decreased, while in CSF, 22 were increased and 6 decreased during the first post-injury week. Key mediators (IL-8 and IL-10) were consistently elevated in both compartments, although some variation was observed between the ECL and PEA platforms. When comparing analytic methods, ECL and PEA showed strong cross-platform correlations for IL-8 and IL-10 in both plasma and CSF, whereas IL-13 exhibited weak, non-significant agreement. Platform-related differences across compartments and time points were also observed. Conclusion Our findings show a marked inflammatory response in severe TBI, with distinct temporal patterns and robust neuroinflammation in CSF. While ECL and PEA showed strong correlations for several mediators, platform-dependent variability was noted. These insights improve our understanding of TBI-induced neuroinflammation and may help refine biomarker-driven prognostic and therapeutic strategies.