Identification of novel key markers that are induced during traumatic brain injury in mice

PeerJ. 2023 Aug 25:11:e15981. doi: 10.7717/peerj.15981. eCollection 2023.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Keywords: Cellular signaling; PBMCs; Traumatic brain injury; ischemia/reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain
  • Brain Injuries, Traumatic* / diagnosis
  • Calcium-Binding Proteins
  • Leukocytes, Mononuclear
  • Mice
  • RNA
  • Reperfusion Injury*

Substances

  • RNA
  • RCN3 protein, mouse
  • Calcium-Binding Proteins

Grants and funding

This work was supported by the support of the National Natural Science Foundation of China (32000509), the Jiangsu University of Basic Science (Natural Science) Research Project (No. 20KJB180003), and the Scientific Research Project of Jiangsu Commission of Health (Z2020002) to Xingjie Ma. Qingbin Zheng was supported by the Social Development Project of Yangzhou Science and Technology Bureau (YZ2020083). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.