Epileptogenesis Induced by Alternate‐site Kindling in Bilateral Hippocampi

Purpose: 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. Methods: 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 μA (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. Results: 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. Conclusions: 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.