An electrophysiological study on the mechanism of seizure generation in rat brain slices : the effect of adenosine on epileptiformactivities.

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Bathing rat brain slice containing hippocampus(HC) and entorhinal cortex(EC) in magnesium-free(0-Mg) medium elicits electrographic seizures. They are eventually replaced by interictal bursts(IIBs), which have been shown to arise in hippocampal area CA3 and suppress seizure generation in EC.We have reported that during this IIB phase, the exposure to hypoxia suppresses IIBs in CA3 and promotes seizure reappearance in EC.These data suggest that hypoxia may play an important role in the transition between IIBs and seizures. On the other hand, it has been reported that adenosine suppresses the neuronal activity during hypoxia. Given these findings, the present study examined the effect of adenosine and its antagonist theophylline on the epileptiform activities in order to investigate the mechanisms underlying the transition from IIBs to seizures in this model.Extracellular recordings were made in area CA3 and EC or HC/EC slices from Sprague-Dawley rats. In the 0-Mg medium, seizures appeared first but eventually they gave way to IIBs in both regions. After the seizures were completely replaced by IIBs, adenosine(50-100muM) was applied to the extracellularsolution. The IIBs in CA3 were suppressed in all the slices tested(n=33), while in EC the seizures reappeared in 28 slices(85%). In the theophylline experiments, hypoxia was introduced by switcihg the oxygenation gas from 95%O_2+5%CO_2 to 30%O_2+65%N_2+5%CO_2 during the IIB phase, then 100muM theophylline was added to the solutino(n=14). The EC-seizures reappeared in the hypoxic condition, however, theophylline blocked the effect and they were replaced by IIBs again.In conclusion, adenosine is one of the modulatory factors withch can promote the transition from IIBs to seizures in this O-Mg/hypoxia model.