Expression of the immediate early genes c-Fos and c-Jun after head injury in man

Abstract

Immediate early genes (IEC) are expressed in a variety of experimental paradigms including cerebral ischemia and trauma. There is a paucity of information on whether the results of laboratory experiments can be extrapolated from animals into man. To examine this further we hypothesised that expression of c-Fos and c-Jun occurs after contusionai head injury in man. We also sought to identify whether there was an association between the level of immediate early gene expression and 1. the outcome one year after head injury, 2. the timing of surgery after head injury. IEC expression was examined using in situ hybridisation and immunocytochemistry in brain tissue therapeutically removed in 14 patients with head injury 6 h to 6 days after contusionai injury. IEC expression was also examined in tissue removed during elective non-traumatic neurosurgery for comparative purposes. Expression of c-fos and c-jun mRNA was observed in 50% and 64% of head-injured patients respectively. Protein immunoreactivity for these lEGs was evident in 67% of head injured patients. The expression of c-Fos and c-Jun was associated with final outcome. Patients with poorer outcomes had higher levels of gene expression (p = 0.08 for c-Fos and p = 0.006 for c-Jun). No correlation between the timing of surgery and the intensity of gene expression was evident in the trauma patients (r2=0.09 and 0.10 for c-Fos and c-Jun respectively). In the non-trauma patients 36% expressed c-fos and 73% expressed c-jun mRNA, with all patients studied expressing c-Fos and c-Jun proteins. We conclude that differential expression of c-Fos and c-Jun occurs in the patients with cerebral contusions. The difference in expression rates between mRNA and protein emphasises the need for analysis of gene products when investigating gene expression. These results support the hypothesis that lEGs may be involved in the pathogenetic mechanisms of contusionai head injury. Observations of IEC expression in human brain injury are important in steering animal experimental programmes towards studies that may yield information directly applicable to human brain injury. [Neurol Res 2000; 22: 138-144]