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. 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.

中文翻译：

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乙醇中毒对小鼠钝性外伤脑损伤外周标志物的不同影响

背景 在小鼠模型和患者中，基于血液的生物标志物已被证明是衡量创伤性脑损伤 (TBI) 严重程度和结果的可靠方法。特别是，神经元特异性烯醇化酶 (NSE)、神经丝光 (NFL) 和 S100 beta (S100B) 已在损伤后的临床环境中进行了研究。乙醇中毒 (EI) 仍然是 TBI 的重要合并症，30-40% 的患者在 TBI 后血液酒精浓度呈阳性。乙醇对用于 TBI 预后和诊断的血液生物标志物的影响仍不清楚。在这项研究中，我们研究了 EI 对 NSE、NFL 和 S100B 的影响以及它们与 TBI 小鼠模型中血脑屏障完整性的相关性。方法 我们采用超灵敏单分子阵列技术和酶联免疫吸附测定法测量 NFL、NSE、TBI 后 3 小时血浆中的 S100B 和 claudin-5 浓度。结果 我们发现 NFL、NSE 和 S100B 在 TBI 后 3 小时增加。有趣的是，乙醇血液浓度与 NSE 呈负相关，但与 NFL 或 S100B 无关。Claudin-5 水平在损伤后增加，但与乙醇预处理相比没有检测到差异。TBI 后 Claudin-5 的增加与 NFL 相关，但与 NSE 或 S100B 无关。结论 乙醇对血流中生物标志物释放的影响不同于不受酒精影响的 TBI。这可能是对人类进行调查的基础。乙醇血液浓度与 NSE 呈负相关，但与 NFL 或 S100B 无关。Claudin-5 水平在损伤后增加，但与乙醇预处理相比没有检测到差异。TBI 后 Claudin-5 的增加与 NFL 相关，但与 NSE 或 S100B 无关。结论 乙醇对血流中生物标志物释放的影响不同于不受酒精影响的 TBI。这可能是对人类进行调查的基础。乙醇血液浓度与 NSE 呈负相关，但与 NFL 或 S100B 无关。Claudin-5 水平在损伤后增加，但与乙醇预处理相比没有检测到差异。TBI 后 Claudin-5 的增加与 NFL 相关，但与 NSE 或 S100B 无关。结论 乙醇对血流中生物标志物释放的影响不同于不受酒精影响的 TBI。这可能是对人类进行调查的基础。