Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (7): 1235-1243.doi: 10.4103/1673-5374.301028

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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). 

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