Detection of hypoxia markers in the cerebellum after a traumatic frontal cortex injury: a human postmortem gene expression analysis

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• 作者：K. Schober ; B. Ondruschka ; J. Dre?ler ; M. Abend
• 关键词：Traumatic brain injury ; Human ; Post mortem ; Gene expression ; Biomarker ; mRNA ; miRNA ; IL ; 6 ; FOSB ; HSPA12B ; HSD11B1 ; miR ; 138 ; miR ; 744 ; miR ; 195 ; miR ; 324 ; 5p
• 刊名：International Journal of Legal Medicine
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：129
• 期：4
• 页码：701-707
• 全文大小：231 KB
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• 作者单位：K. Schober (1)
  B. Ondruschka (2)
  J. Dre?ler (2)
  M. Abend (3)
  
  1. German Air Force Center for Aerospace Medicine, Postfach 1264/KFL, 82242, Fürstenfeldbruck, Germany
  2. Institute of Legal Medicine, Medical Faculty, University of Leipzig, Johannisallee 28, 04103, Leipzig, Germany
  3. Bundeswehr Institute of Radiobiology, Neuherbergstra?e 11, 80937, Munich, Germany
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Forensic Medicine
  Medical Law
  Medicine/Public Health, general
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1437-1596

文摘

Purpose The response to traumatic brain injury (TBI) is complex and induces various biological pathways in all brain regions that contribute to bad outcomes. The cerebellar hypoxia after a frontal cortex injury may potentiate the pathophysiological impacts of TBI. Therefore, a gene expression analysis was conducted to determine the influence of hypoxia on TBIs. Material and methods Total RNA, including microRNAs, was isolated from the cerebellum of individuals who had died from severe frontal cortex injuries or due to natural causes of death (reference group). Results From a total of 19,596 genes, an average of 59.56?% messenger RNAs (mRNAs) appeared expressed with 42 of them showing significant >2-fold differences of upregulated (n--8) and downregulated (n--4) genes. The validity of 14 candidate genes (with low p values and high fold differences or based on cited literature) was confirmed using qRT-PCR (Spearman correlation r 2--.93). Only four genes appeared to be either upregulated (FOSB and IL6) or downregulated (HSD11B1 and HSPA12B). From a total of 667 microRNAs, altogether, 248 microRNAs appeared expressed with 13 of them showing significant differences in the mean gene expression. The combination of two mRNAs (HSPA12B/FOSB or IL6/HSD11B1) or two microRNAs (either miR-138/miR-744 or miR-195/miR-324-5p) completely discriminated both groups, a finding unaltered by potential confounders such as age at biosampling, survival time, and the postmortem interval. Conclusions Cerebellar hypoxia markers are important to understand the pathophysiology of TBIs and could be used for therapeutic strategies or forensic purposes, e.g., to assess the severity of a brain injury.