海馬キンドリング形成過程における発作閾値の2相性変化

A BIPHASIC CHANGE OF THE SEIZURE-THRESHOLD IN KINDLING SEIZURE DEVELOPMENT INDUCED WITH LOW-FREQUENCY ELECTRICAL STIMULATIONS

　抄録　低頻度電気刺激法を用いてキンドリング形成過程における発作閾値の変化を詳細に検討した。7頭のネコを用い腹側海馬にパルス間間隔30msecの低頻度電気刺激を1日1回加えた。発作閾値はてんかん発作波誘発にまで要するパルス数（pulse-number threshold）を用いた。平均36.5回の刺激でキンドリングが完成した。pulse-number thresholdは初めの平均3.8回の刺激で急激に減少し，しばらく一定値を呈した後徐々に増加する二相性変化を示した。これらの一連の変化はてんかんの成因，治療を考える上で興味深い所見と思われる。

Seven cats were stimulated once a day with low-frequency electrical stimulations to assess the serial changes of development. Each animal had been implanted stereotaxically with a stimulating electrode into the left-side ventral hippocampus and with recording electrodes into the right-sidevantral hippocumpus, the bilateral dorsal hippo-cumpus. We applied the stimulations at 10: 00 AM, bipolarly with 2 mA-biphasic square-wave pulses (1 msec durations). The pulse-interval was set at 300 msec. If epileptic afterdischarge could not be triggered on EEG with this pulse-interval, a 100 msec-interval stimulation was applied after 15 min-rest period. The number of stimulating pulses required for a triggering of afterdischarge was defined as pulse-number threshold (PNT) which was used as an indicator of the seizure-threshold. The duration of each seizure on EEG (afterdischarge duration, ADD) was also recorded and the seizure-related behaviors were classified into 5 stages as follows : 1, staring or immobi-lity; 2 appearance of facial twitching or head noddings ; 3, tonic convulsions of the right-side fore-paw or a head turning toward the righ-side ; 4, generalized clonic convulsions ; 5, generalized convulsions with a falling down. The kindling procedure completed within a mean of 36. 5 days, and all the animals presented stage-5 seizures. At the completion of kindling, PNT was deter-mined at 10. 5±1.8 (mean-± SE). During the kindl-ing process PNT showed a sudden decrease in the intial part of stage-1 (within a mean of 3. 8 days) and a gradual increase from stage-3 to stage-5. ADD showed a simple increasing func-tion of the development of seizure-stage. We itemized the major interesting findings of this study as follows. First, such a biphasic change of the seizure-threshold in kindling seizure deve-lopment has not been definitely reported as far as we know. We consider this phenomenon to be important in deepening the understanding of seizure generation. Second, this study and other previous studies showed that the development of seizure occurred after a decrease of seizure-thre-shold of the stimulating site, suggesting that a high-susceptibility of epileptic focus is needed for a development of triggered seizures.