Experimental brain injury induces differential expression of tumor necrosis factor-alpha mRNA in the CNS

In the present study, we examined the expression of tumor necrosis factor-alpha (TNF-alpha) mRNA in specific brain regions following experimental lateral fluid percussion traumatic brain injury (TBI) in rats. Adult Sprague-Dawley rats (n = 42) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) and subjected to lateral fluid percussion brain injury of moderate severity (2.4 atm.) centered over the left temporoparietal cortex, or 'sham' treatment (anesthesia and surgery without injury). Animals were killed by decapitation at 1, 6 or 24 h post injury, brains removed, and tissue samples of left (injured) parietal cortex (LC), right parietal cortex (RC), left adjacent cortex (LA), right adjacent cortex (RA), left hippocampus (LH) and right hippocampus (RH) were prepared. Total RNA was isolated and Northern blot hybridization was performed. TNF-alpha mRNA is expressed as the percent relative radioactivity of macrophage (positive control) RNA. In sham or naive animals, no consistent changes in expression of TNF-alpha mRNA were observed in any of the six brain areas at any times (less than 5%). A marked increase of TNF-alpha mRNA expression was observed in LH (104 +/- 17, P < 0.05 compared with sham), LC (105 +/- 21, P < 0.05) and LA (69 +/- 8, P < 0.01) in the traumatized hemisphere 1 h following injury. An increased TNF-alpha mRNA expression was also observed in LH (46 +/- 8, P < 0.05), LC (30 +/- 3, P < 0.01) and LA (32 +/- 3, P < 0.01) at 6 h which resolved by 24 h following injury. In the contralateral hemisphere, expression of TNF-alpha mRNA was increased in RH (46 +/- 2, P < 0.01) at 1 h and in RA (26 +/- 6%, P < 0.05) at 6 h. These results indicate that following parasagittal fluid percussion brain injury, the temporal expression of TNF-alpha mRNA is altered in specific brain regions, including those of the non-traumatized hemisphere. Post-traumatic alteration in gene expression of TNF-alpha might play an important role in both the acute and regenerative response to CNS trauma.