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

乙醇中毒对小鼠钝性脑损伤外周标志物的不同影响

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作者:Zhenghui Li, Jin Zhang, Steffen Halbgebauer, Akila Chandrasekar, Rida Rehman, Albert Ludolph, Tobias Boeckers, Markus Huber-Lang, Markus Otto, Francesco Roselli, Florian Olde Heuvel

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, neuron-specific 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.

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.

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.

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