INCREASED EXPRESSION OF C-FOS MESSENGER-RNA AND AP-1 TRANSCRIPTION FACTORS AFTER CORTICAL IMPACT INJURY IN RATS

Levels of c-fos mRNA and AP-1 transcription factors co-expression were measured in a controlled lateral cortical impact model of traumatic brain injury (TBI) in rats. Ipsilateral cerebral cortex and bilateral hippocampal c-fos mRNA increases were revealed by in situ hybridization after lateral cortical impact injury. Based on regional in situ hybridization data, we employed semi-quantitative RT-PCR methods to study the temporal profile of changes in the ipsilateral cortex at the site of injury. We found that TBI produces transient increases of c-fos mRNP; expression in the ipsilateral cerebral cortex at 5 min postinjury, which peaks at 1 h postinjury and subsides by 1 day postinjury. Gel shift nuclear protein binding assays showed that AP-1 transcription factor binding was robustly increased in injured cerebral cortex at 1 h, 3 h, 5 h and 1 day after injury. These data indicate that TBI can produce significant increases in c-fos expression and subsequent upregulation of the AP-1 transcription factors. Thus, AP-1 transcription factors modulation of downstream gene expression may be an important component of pathophysiological responses to TBT.