Severe TBI patients exhibit dynamic, compartmentalized inflammatory responses in blood and CSF, with platform-dependent biomarker detection.

Traumatic brain injury (TBI) is a devastating condition leading to high mortality and long-term disability, primarily due to its complex and heterogeneous pathophysiology. Current treatments are largely supportive, lacking targeted interventions for the intricate cascade of events post-injury. Inflammation is a central driver of secondary brain damage in TBI, yet the early dynamics of inflammatory mediators in both blood and cerebrospinal fluid (CSF) are not fully understood. Furthermore, the agreement between different assay platforms used for biomarker quantification, such as electrochemiluminescence (ECL) and proximity extension assay (PEA), has rarely been directly compared, posing challenges for consistent biomarker interpretation.

This prospective observational study recruited 21 adults with severe TBI and 11 orthopedic patients with minor extremity fractures as controls. Plasma and CSF samples were collected from TBI patients at two time points: days 1-3 and days 4-8 post-injury. Inflammatory mediator levels were quantified using two distinct platforms: ECL (measuring 11 mediators) and PEA (measuring 45 mediators). The primary endpoints included characterizing group differences, temporal changes in mediator levels, and assessing inter-platform agreement for key inflammatory biomarkers across both compartments.

During the first week post-injury, severe TBI patients demonstrated a significant inflammatory response. In plasma, 13 inflammatory mediators were increased, while 3 decreased. The CSF showed an even more pronounced response, with 19 mediators increased and 3 decreased. Key inflammatory mediators, including IL-6, IL-8, and IL-10, were consistently elevated in both blood and CSF compartments. When comparing the two analytical methods, ECL and PEA exhibited strong cross-platform correlations for IL-8 and IL-10 in both plasma and CSF. However, IL-13 showed a weak, non-significant correlation between platforms. Importantly, the study revealed limited interchangeability between the ECL and PEA platforms, with platform-related differences observed across compartments and time points. This underscores the complexity of the inflammatory response and the nuances of biomarker detection.

Severe TBI is associated with a marked, temporal, and compartmentalized inflammatory response during the first week post-injury, particularly evident in the CSF.