Department of Acupuncture and Moxibustion, College of Traditional Chinese Medicine, Jinan University, 510632 Guangzhou, Guangdong, China.
Medical Administration Division, The First Affiliated Hospital of Jinan University, 510630 Guangzhou, Guangdong, China.
J Integr Neurosci. 2023 Feb 20;22(2):44. doi: 10.31083/j.jin2202044.
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.
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.
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.
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.
创伤性脑损伤（TBI）是一种常见的脑损伤，发病率和死亡率都很高。TBI 引发的复杂损伤级联反应可导致认知障碍等永久性神经功能障碍。为了为阐明 TBI 潜在的分子机制提供新的见解，本研究系统分析了 TBI 亚急性期大鼠海马的转录组数据。
从基因表达综合数据库（GEO）下载了两个数据集（GSE111452 和 GSE173975）。进行了系统的生物信息学分析，包括差异表达基因（DEGs）分析、基因集富集分析（GSEA）、GO 富集分析、KEGG 通路分析、蛋白质-蛋白质相互作用（PPI）网络构建和关键基因识别。此外，还进行了苏木精和伊红（HE）、尼氏和免疫组织化学染色，以评估 TBI 大鼠模型中受伤的海马。通过生物信息学分析鉴定的关键基因在 mRNA 表达水平上得到验证。
两个数据集中共有 56 个 DEGs 存在重叠。GSEA 结果表明，MAPK 和 PI3K/Akt 通路、焦点黏附和细胞衰老显著富集。GO 和 KEGG 分析表明，共同的 DEGs 主要与免疫和炎症过程相关，包括抗原加工和呈递、白细胞介素介导的免疫、适应性免疫反应、淋巴细胞介导的免疫、吞噬体、溶酶体以及补体和凝血级联反应。构建了共同 DEGs 的 PPI 网络，鉴定出 15 个关键基因。在共同 DEGs 中，我们鉴定出了两个转录共因子和 15 个免疫相关基因。GO 分析结果表明，这些免疫相关的 DEGs 主要富集在与小胶质细胞、星形胶质细胞和巨噬细胞等多种细胞激活相关的生物学过程中。HE 和尼氏染色结果表明海马神经元明显损伤。免疫组织化学染色显示受伤海马中 Iba1 阳性细胞数量明显增加。关键基因的 mRNA 表达水平与转录组数据一致。
本研究强调了 TBI 相关海马损伤中潜在的病理过程。本研究中鉴定的关键基因可能成为新的生物标志物和治疗靶点，加速开发治疗 TBI 相关海马损伤的有效治疗方法的步伐。
