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

Cell stimulation which leads to degeneration triggers a prolonged wave of i mmediate early gene (IEG) transcription that correlates with neuronal demis e. In order to determine the relevance of the prolonged IEG response to hum an traumatic brain injury, we analyzed IEG mRNA levels in brain tissue isol ated following a controlled penetrating injury and an injection of the exci totoxin Quinolinic acid (QA), as well as from tissue recovered during routi ne neurosurgery for trauma. Total RNA was extracted from tissue and subject ed to Northern analysis of IEG mRNAs (c-fos and zif/268). Both models produ ced rapid and prolonged waves of IEG transcription that appeared to correla te with the severity of injury. Increases in zif/268 mRNA were observed wit hin 1 h with levels reaching their peak at 6 h following excitotoxic injury and 3 h following a controlled penetration. In general, human traumatic br ain injury resulted in variable increases in IEG mRNA levels following trau matic injury with the largest IEC mRNA increases observed in tissue collect ed 0-10 h after injury. This post-injury time corresponds to the peak of th e prolonged IEG response observed in rodents following excitotoxic injury. Comparisons were made in IEG response between rodent frontal cortex and hum an cortex, because the majority of the human tissue originated from the cer ebral cortex. These results further support the hypothesis that prolonged I EG 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.