Epileptogenesis induced by alternate-site kindling in bilateral hippocampi

Alternate-site kindling (AK), which has been known to induce so-called kindling antagonism, was performed in the bilateral hippocampi to reveal neural mechanisms underlying hippocampal kindling.

Ten adult rabbits were used. Daily kindling stimulation consisted of a 1- s train of 50 pulses (pulse duration, 1 ms) of 80 to 200 microA (base-to-peak), which was higher than the afterdischarge (AD) threshold. The concurrent alternating stimulations were delivered to the right and left hippocampus once every 24 h.

All animals developed a stage 5 convulsion with a mean of 28.1 +/- 3.3 (mean +/- SEM) stimulations. The right and left hippocampus received 14.8 +/- 1.7 and 14.6 +/- 1.6 stimulations, respectively. Behavioral stages induced by stimulation of the right or left hippocampus evolved to generalized seizures along a similar course. Kindling antagonism was not observed. The two sides showed similar increases in AD duration, and similar chronologic changes in interictal discharge (IID) frequency. Simple A-type IID and complex types of IID appeared at higher rates, whereas simple B-type IID remained at a relatively low level.

The present AK procedure did not induce kindling antagonism, but it induced progression of kindling manifestations. The origin of simple B-type IID is known to be in the contralateral side, and its intracellular counterpart corresponds to a sequence of small depolarization followed by large hyperpolarization, suggesting that plastic changes in the feed-forward inhibitory system play an important role in hippocampal kindling.