Department of Intensive Care, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Department of Lung, the Third People's Hospital of Yangzhou, Yangzhou, China.
PeerJ. 2023 Aug 25;11:e15981. doi: 10.7717/peerj.15981. eCollection 2023.
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.
创伤性脑损伤（TBI）已成为一个日益严重的公共卫生问题，但尚未得到充分研究，特别是在 TBI 期间大脑细胞行为的机制方面。
在这项研究中，我们使用短暂性大脑中动脉闭塞（tMCAO）策略建立了缺血/再灌注（I/R）脑损伤小鼠模型。然后，对额叶进行 RNA 测序，以筛选 TBI 期间的关键诱导物。为了进一步验证所选基因，我们从在扬州大学附属医院重症监护病房（ICU）就诊的 24 小时内的 TBI 患者中收集外周血单核细胞（PBMC），并使用 RT-qPCR 分析基因表达。最后，应用接收器操作特征（ROC）曲线和与细胞衰老标志物的共表达来评估基因的预测价值。
基于在 TBI 中的新颖性及其在细胞凋亡和细胞衰老信号通路中的意义，从 RNA 测序中筛选出了总共 6 个基因。与在医院进行体检的健康志愿者相比，对患者 PBMC 的 RT-qPCR 分析表明，在 TBI 后这 6 个基因均上调。ROC 曲线下面积（AUC）均>0.7，并且这 6 个基因与衰老标志物的共表达评分均呈显著正相关。因此，我们确定了 TGM1、TGM2、ATF3、RCN3、ORAI1 和 ITPR3 作为在 TBI 期间诱导的新型关键标志物，这些标志物也可能作为 TBI 进展的潜在预测因子。
