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Studies of qingyangshen (I): Differential expression of hippocampal c-fos proto-oncogene during kainic acid induced acute and chronic seizures.

We previously reported that Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, had therapeutic effect on kainic acid (KA) induced experimental seizures (see JTCM 13 (4): 281-286, 1993 for reference). To investigate the mechanisms underlying the anticonvulsant action of QYS, we analyzed the modulatory effect of QYS on rat hippocampal c-fos proto-oncogene expression during KA-induced epileptogenesis in this and the following paper. The expression of hippocampal c-fos gene during KA-induced seizures were examined first. Rats were intraperitoneally injected with kainic acid (KA, 12 mg/kg) and hippocampal c-fos mRNA level was determined by Northern blot analysis during both acute (within one day after KA injection) and chronic (15 days after KA treatment) seizures. A mild increase in hippocampal c-fos mRNA level was observed 30 min after KA injection (being 1.98 +/- 0.70 times of control level), which corresponded temporally to the occurrence of the first limbic seizures. There was an 11.02 +/- 3.33 fold maximal induction of c-fos mRNA at 2 h after KA administration, which remained relatively stable even when behavioral seizures continued to aggravate 4 h after KA treatment. Twelve hours after KA administration, c-fos mRNA in the hippocampus returned to control level when acute seizures began to gradually disappear. In contrast, the induction of hippocampal c-fos mRNA during chronic seizures was inhibited significantly, being reduced by 55.40% compared to control. This suggested that c-fos is in different functional states at acute and chronic stages of epileptogenesis induced by KA.