Fluid proteomics of CSF and serum reveal important neuroinflammatory proteins in blood–brain barrier disruption and outcome prediction following severe traumatic brain injury: a prospective, observational study

Abstract Background Severe traumatic brain injury (TBI) is associated with blood–brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform multiplex screening of enriched inflammatory proteins in blood cerebrospinal fluid (CSF) order study their role BBB disruption, neuroinflammation long-term functional outcome TBI patients healthy controls. Methods conducted prospective, observational on 90 severe 15 control subjects. Clinical data, Glasgow Outcome Score, was collected after 6–12 months. utilized suspension bead antibody array analyzed FlexMap 3D Luminex platform characterize 177 unique matched CSF serum samples. In addition, we assessed using the CSF-serum albumin quotient ( Q A ), performed Apolipoprotein E-genotyping as latter has been linked function absence trauma. employed pathway-, cluster-, proportional odds regression analyses. Key findings were validated samples from an independent cohort. Results had upregulation structural CNS pathways both serum. total, 114 correlated , among which top-correlated complement proteins. cluster analysis revealed protein levels be strongly integrity, but not carriage E4-variant. Among cluster-derived proteins, innate immune upregulated. Forty emanated novel predictors clinical outcome, that individually explained ~ 10% additional model variance. significantly different between intact or disrupted BBB, C9 p = 0.014, ? R 2 7.4%) factor B 0.003, 9.2%) also following step-down modelling. Conclusions This represents largest concomitant proteomic profiling so far reported TBI, providing substantial support notion markers, including activation, predicts outcome. Individual identified here could potentially serve refine current biomarker modelling represent treatment targets TBI.