Patterns of immediate early gene mRNA expression following rodent and human traumatic brain injury

被引:30
作者
Dutcher, SA
Underwood, BD
Walker, PD
Diaz, FG
Michael, DB
机构
[1] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA
[2] Wayne State Univ, Sch Med, Dept Neurol Surg, Detroit, MI 48201 USA
关键词
zif/268; human brain injury; gene expression; cerebral cortex;
D O I
10.1080/01616412.1999.11740924
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Cell stimulation which leads to degeneration triggers a prolonged wave of immediate early gene (IEG) transcription that correlates with neuronal demise. In order to determine the relevance of the prolonged IEG response to human traumatic brain injury, we analyzed IEG mRNA levels in brain tissue isolated following a controlled penetrating injury and an injection of the excitotoxin Quinolinic acid (QA), as well as from tissue recovered during routine neurosurgery for trauma. Total RNA was extracted from tissue and subjected to Northern analysis of IEG mRNAs (c-fos and zif/268). Both models produced rapid and prolonged waves of IEG transcription that appeared to correlate with the severity of injury. Increases in zif/268 mRNA were observed within 1 h with levels reaching their peak at 6 h following excitotoxic injury and 3 h following a controlled penetration. In general, human traumatic brain injury resulted in variable increases in IEG mRNA levels following traumatic injury with the largest IEC mRNA increases observed in tissue collected 0-10 h after injury. This post-injury time corresponds to the peak of the prolonged IEG response observed in rodents following excitotoxic injury. Comparisons were made in IEG response between rodent frontal cortex and human cortex, because the majority of the human tissue originated from the cerebral cortex. These results further support the hypothesis that prolonged IEG transcription serves as a marker of traumatic brain injury and may play a role in neurodegeneration and/or glial activation. Moreover, observations of similar IEC patterns of expression reinforces the importance of rodent models of brain injury providing useful information directly applicable to human brain injury.
引用
收藏
页码:234 / 242
页数:9
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