Differential effect of ethanol intoxication on peripheral markers of cerebral injury in murine blunt traumatic brain injury

Background:Blood-based biomarkers have proven to be a reliable measure of the severity and outcome of traumatic brain injury(TBI)in both murine models and patients.In particular,neuronspecific enolase(NSE),neurofilament light(NFL)and S100 beta(S100B)have been investigated in the clinical setting post-injury.Ethanol intoxication(EI)remains a significant comorbidity in TBI,with 30–40%of patients having a positive blood alcohol concentration post-TBI.The effect of ethanol on blood-based biomarkers for the prognosis and diagnosis of TBI remains unclear.In this study,we investigated the effect of EI on NSE,NFL and S100B and their correlation with blood–brain barrier integrity in a murine model of TBI.Methods:We used ultra-sensitive single-molecule array technology and enzyme-linked immunosorbent assay methods to measure NFL,NSE,S100B and claudin-5 concentrations in plasma 3 hours post-TBI.Results:We showed that NFL,NSE and S100B were increased at 3 hours post-TBI.Interestingly,ethanol blood concentrations showed an inverse correlation with NSE but not with NFL or S100B.Claudin-5 levels were increased post-injury but no difference was detected compared to ethanol pretreatment.The increase in claudin-5 post-TBI was correlated with NFL but not with NSE or S100B.Conclusions:Ethanol induces an effect on biomarker release in the bloodstream that is different from TBI not influenced by alcohol.This could be the basis of investigations into humans.