SEQUENTIAL EXPRESSION OF C-FOS PROTOONCOGENE, TNF-ALPHA, AND DYNORPHIN GENES IN SPINAL-CORD FOLLOWING EXPERIMENTAL TRAUMATIC INJURY

Reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate dynamic changes in levels of c-fos protooncogene, tumor necrosis factor alpha (TNF-alpha), and preprodynorphin messenger ribonucleic acid (mRNA) isolated from individual segments (T1 to T12) of rat spinal cord following graded impact trauma (50 or 100 g/cm) to the T9 segment of pentobarbital-anesthetized rats. Trauma caused elevation of c-fos mRNA at the trauma site by 30 min after injury that was related to injury severity. At this time, increased levels of TNF-alpha (but not of preprodynorphin) mRNA were also found. By 24 h, c-fos and TNF-alpha mRNA had returned to normal levels at trauma site, but were now increased at more distal segments (T5 and T12). At 4 h after trauma, induction of preprodynorphin mRNA was detected at the trauma site; levels continued to be elevated at 24 h when they were also detected at T5 and T12. Increases for each mRNA were greater for severe as compared to moderate trauma. The injury dose- and time-dependent changes in c-fos, TNF-alpha, and preprodynorphin gene expression suggest that their respective proteins are synthesized in response to trauma, and may play a part in the secondary injury response. Later accumulation of message distant from the trauma site may reflect a progression of delayed damage along the spinal cord.