中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1235-1243.doi: 10.4103/1673-5374.301028

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑创伤大小鼠大脑皮质的比较转录组学分析

  

  • 出版日期:2021-07-15 发布日期:2021-01-07
  • 基金资助:

    基金资助：国家自然科学基金(8147123；81771327)、中枢神经系统损伤基础科学与临床转化研究平台建设、北京市卫生委员会2020年预算资助项目(PXM2020_U000002)。

Comparative transcriptomic analysis of rat versus mouse cerebral cortex after traumatic brain injury

Meng-Shi Yang1, 2, #, Xiao-Jian Xu1, #, Bin Zhang1, 2, Fei Niu1, Bai-Yun Liu1, 2, 3, 4, *   

  1. 1Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; 2Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 3Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing, China; 4China National Clinical Research Center for Neurological Diseases, Beijing, China 
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Bai-Yun Liu, M.D., liubaiyun1212@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81471238, 81771327 (both to BYL), Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform, Budget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (to BYL). 

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摘要：

创伤性脑损伤继发性损伤机制的高度异质性严重阻碍了创伤性脑损伤治疗的发展。靶向创伤性脑损伤过程中跨物种的共有机制，有可能成为创伤性脑损伤治疗的新策略。为此，实验首次进行了跨物种转录组比较，对SD大鼠和C57/BL6小鼠采用控制性大脑皮质打击法建立急性创伤性脑损伤模型，观察两组动物在急性创伤性脑损伤后的共同继发性损伤机制。(1)小鼠转录组测序数据是从NCBI公共数据库GEO数据库下载获取(ID：GSE79441)；(2)创伤性脑损伤后24 h收集各组损伤灶周边大脑皮质组织用于转录组分析；(3)差异表达基因功能分析表明，创伤性脑损伤后两个物种之间的共同特征主要涉及固有免疫应答的调节和激活，如补体级联反应、Toll样和Nod样受体信号通路，随后的基因集富集分析则进一步证实上述结果；(4)转录因子分析显示，STAT，BZIP，RHD和IRF转录因子家族在创伤性脑损伤的病理过程中发挥着核心的转录调控作用，同时这些转录因子家族也与炎症反应密切相关；(5)上述结果表明，靶向固有免疫应答有可能是一种具有潜在价值的创伤性脑损伤治疗方式。实验已于2018-06-06通过中国北京市神经外科研究所动物伦理委员会的审查(No. 201802001)。

https://orcid.org/0000-0001-8204-2623 (Bai-Yun Liu)

关键词:

脑外伤, 继发性损伤, 跨物种比较, 转录组, 炎症, 转录因子, 先天免疫, 基因集富集分析, 认知障碍, 神经退行性疾病

Abstract: The heterogeneity of traumatic brain injury (TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients. Targeting common processes across species may be an innovative strategy to combat debilitating TBI. In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact. The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus (ID: GSE79441) at the National Center for Biotechnology Information. For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI. Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways. These findings were further corroborated by gene set enrichment analysis. Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription (STAT), basic leucine zipper (BZIP), Rel homology domain (RHD), and interferon regulatory factor (IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation. These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI. The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee (approval No. 201802001) on June 6, 2018.

Key words: cognitive impairment, cross-species comparison, gene set enrichment analysis, inflammation, innate immune, neurodegenerative disease, secondary injury, transcription factor, transcriptome, traumatic brain injury