Identification of novel key markers that are induced during traumatic brain injury in mice.
Identification of novel key markers that are induced during traumatic brain injury in mice.
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作者：
Li Y;Li N;Luan C;Pei Y;Zheng Q;Yan B;Ma X;Liu W
创伤性脑损伤已成为一个日益严重的公共卫生问题，但目前对其研究还不够深入，尤其是对其脑细胞行为机制的研究还不够深入。本研究采用短暂性大脑中动脉闭塞(TMCAO)策略建立小鼠脑缺血/再灌注(I/R)损伤模型。然后，对额叶进行RNA测序，以筛选脑损伤期间的关键诱导物。为了进一步验证所选择的基因，我们采集了扬州大学附属医院重症监护室(ICU)患者在24小时内的外周血单核细胞(PBMC)，并用RT-qPCR方法分析了这些基因的表达。最后，利用受试者操作特征(ROC)曲线和与细胞衰老标志物的共表达来评估这些基因的预测价值。根据它们在脑损伤中的新颖性以及与细胞凋亡和细胞衰老信号的关系，从RNA测序中筛选出6个基因。对患者外周血单个核细胞的RT-qPCR分析表明，与到医院体检的健康志愿者相比，这六个基因在脑外伤过程中都有上调。ROC曲线下面积(AUC)均为-0.7，6个基因与衰老标记的共表达得分均为显著正。因此，我们确定TGM1、TGM2、ATF3、RCN3、ORAI1和ITPR3是在脑损伤过程中诱导的新的关键标记，这些标记也可能作为预测脑损伤进展的潜在指标。
Traumatic brain injury (TBI) has emerged as an increasing public health problem but has not been well studied, particularly the mechanisms of brain cellular behaviors during TBI. In this study, we established an ischemia/reperfusion (I/R) brain injury mice model using transient middle cerebral artery occlusion (tMCAO) strategy. After then, RNA-sequencing of frontal lobes was performed to screen key inducers during TBI. To further verify the selected genes, we collected peripheral blood mononuclear cells (PBMCs) from TBI patients within 24 h who attended intensive care unit (ICU) in the Affiliated Hospital of Yangzhou University and analyzed the genes expression using RT-qPCR. Finally, the receiver operator characteristic (ROC) curves and co-expression with cellular senescence markers were applied to evaluate the predictive value of the genes. A total of six genes were screened out from the RNA-sequencing based on their novelty in TBI and implications in apoptosis and cellular senescence signaling. RT-qPCR analysis of PBMCs from patients showed the six genes were all up-regulated during TBI after comparing with healthy volunteers who attended the hospital for physical examination. The area under ROC (AUC) curves were all >0.7, and the co-expression scores of the six genes with senescence markers were all significantly positive. We thus identified TGM1, TGM2, ATF3, RCN3, ORAI1 and ITPR3 as novel key markers that are induced during TBI, and these markers may also serve as potential predictors for the progression of TBI.
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