IMR Press / JIN / Volume 22 / Issue 2 / DOI: 10.31083/j.jin2202044
Open Access Original Research
Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation
Hai Zeng1,†Sisi Zhao1,†Zhao Pang2,†Shiqi Wang1Luxi Cao1,*Yimin Zhang1,*
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1 Department of Acupuncture and Moxibustion, College of Traditional Chinese Medicine, Jinan University, 510632 Guangzhou, Guangdong, China
2 Medical Administration Division, The First Affiliated Hospital of Jinan University, 510630 Guangzhou, Guangdong, China
*Correspondence: (Luxi Cao); (Yimin Zhang)
These authors contributed equally.
J. Integr. Neurosci. 2023, 22(2), 44;
Submitted: 25 June 2022 | Revised: 27 September 2022 | Accepted: 30 September 2022 | Published: 20 February 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Traumatic brain injury (TBI) is a common brain injury with a high morbidity and mortality. The complex injury cascade triggered by TBI can result in permanent neurological dysfunction such as cognitive impairment. In order to provide new insights for elucidating the underlying molecular mechanisms of TBI, this study systematically analyzed the transcriptome data of the rat hippocampus in the subacute phase of TBI. Methods: Two datasets (GSE111452 and GSE173975) were downloaded from the Gene Expression Omnibus (GEO) database. Systematic bioinformatics analyses were performed, including differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) network construction, and hub gene identification. In addition, hematoxylin and eosin (HE), Nissl, and immunohistochemical staining were performed to assess the injured hippocampus in a TBI rat model. The hub genes identified by bioinformatics analyses were verified at the mRNA expression level. Results: A total of 56 DEGs were shared in the two datasets. GSEA results suggested significant enrichment in the MAPK and PI3K/Akt pathways, focal adhesion, and cellular senescence. GO and KEGG analyses showed that the common DEGs were predominantly related to immune and inflammatory processes, including antigen processing and presentation, leukocyte-mediated immunity, adaptive immune response, lymphocyte-mediated immunity, phagosome, lysosome, and complement and coagulation cascades. A PPI network of the common DEGs was constructed, and 15 hub genes were identified. In the shared DEGs, we identified two transcription co-factors and 15 immune-related genes. The results of GO analysis indicated that these immune-related DEGs were mainly enriched in biological processes associated with the activation of multiple cells such as microglia, astrocytes, and macrophages. HE and Nissl staining results demonstrated overt hippocampal neuronal damage. Immunohistochemical staining revealed a marked increase in the number of Iba1-positive cells in the injured hippocampus. The mRNA expression levels of the hub genes were consistent with the transcriptome data. Conclusions: This study highlighted the potential pathological processes in TBI-related hippocampal impairment. The crucial genes identified in this study may serve as novel biomarkers and therapeutic targets, accelerating the pace of developing effective treatments for TBI-related hippocampal impairment.

traumatic brain injury
bioinformatics analysis
hub gene
81873362/National Natural Science Foundation of China
82174483/National Natural Science Foundation of China
82205249/National Natural Science Foundation of China
2021A1515011219/Natural Science Foundation of Guangdong Province
2021A1515110146/Natural Science Foundation of Guangdong Province
2022M710912/China Postdoctoral Science Foundation
20231086/Administration of Traditional Chinese Medicine of Guangdong Province
Fig. 1.
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