Abstract
BackgroundNeuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.MethodsTBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.ResultsJugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood.ConclusionsSystemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations.Graphical abstract
Highlights
Traumatic brain injury (TBI) is a devastating condition, with an increasing morbidity and mortality [1, 2]
A recent study in mice exposed to Streptococcus pneumoniae and to either traumatic brain injury (TBI) or sham surgery showed that brain-injured mice were unable to demonstrate an appropriate immune response due to impaired monocytic function in both acute and chronic stages of TBI which resulted in greater pulmonary bacterial loads [10]
Apart from a more substantial decrease in C-reactive protein (CRP) in the intervention group compared to the control group, there were no significant differences between the groups in terms of inflammatory markers
Summary
Traumatic brain injury (TBI) is a devastating condition, with an increasing morbidity and mortality [1, 2]. Secondary injury mechanisms play a major role in patient deterioration [3], and of these pathologies neuroinflammation is acknowledged as being one of the main drivers [4]. Ventilator-associated pneumonia (VAP) is present in up to 36% of TBI cases and is associated with a longer hospital stay and increased morbidity [11]. Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition
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