EXPRESSION OF C-FOS AND HSP70 MESSENGER-RNA AFTER TRAUMATIC BRAIN INJURY IN TRANSGENIC MICE OVEREXPRESSING CUZN-SUPEROXIDE DISMUTASE

The aim of this study was to determine the role of oxidative stress on c-fos and hsp70 gene expression in transgenic (Tg) mice overexpressing CuZn-superoxide dismutase (SOD-l) following traumatic brain injury (TBI). hsp70 mRNA, as investigated using in situ hybridization, was induced around the lesion at 4 and 24 h, but not at 1 and 48 h, in both Tg and non-transgenic (nTg) mice littermates. The degree of hsp70 induction was somewhat greater in nTg than Tg mice at 4 and 24 h after TBI. c-fos mRNA was induced throughout cortex, hippocampus, caudate putamen and the ventricular wall in Tg and nTg mice. TBI induced c-fos bilaterally in the cortex in both animals. There was a time-dependent difference in cortical c-fos expression between nTg and Tg mice. The induction of c-fos mRNA in the striatum was greater in nTg at 24 h and decreased in both animals by 48 h. Edema of the injured cortex was significantly attenuated in Tg mice at all time points (1-48 h). These data show that the degree of hsp70 induction and the degree, extent, and duration of c-fos induction produced by TBI are affected by levels of superoxide dismutase activity. It is proposed that superoxide radicals affect spreading depression and brain edema produced by TBI and that this effect may either directly or indirectly modulate the expression of the c-fos and hsp70 genes after TBI.