A NEW MODEL OF EPILEPSY : A SMALL EPILEPTIC Focus BY MICROINJECTION OF KAINIC ACID INTO THE UNILATERAL HIPPOCAMPUS IN CATS Mitsunobu Kaijima 1 , Tatsuya Tanaka 1 , Gou Daita 1 , Shoichiro Ohgami 1 , Yukichi Yonemasu 1 1Department of Neurosurgery, Asahikawa Medical College pp.1133-1140
Published Date 1981/11/1
DOI https://doi.org/10.11477/mf.1406204848
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Kainic acid (KA) is a potent analogue of gluta-mate, of which two major effects, neurotoxic (neurodegenerative) and neuroexciting, have been generally accepted. In regard to the former effect, many studies have been reported including a model of Huntington's chorea which was produced by means of microinjection of KA into the striata ofrats. The latter effect is important in the produc-tion of experimental epilepsy. In 1979 Ben-Ari et al reported a new model of focal status epilepticus by intra-amygdaloid application of KA in rats. These two contradictory effects, neurodegenerative and neuroexciting, are explained as a serial changes of neurous to chemical action of KA, that is, KA interacts with glutamate receptor resulting in prolonged depolarization and this chronic excitation would lead to irreversible ionic imbalance resulting in cell death.

In this study, KA (12μg dissolved in 6μl pho-sphate buffer) was injected into unilateral hip-pocampus of chronic cats, and electrophysiological and clinical features were observed for 14 to 40 days. Phosphate buffer was injected into uni-lateral hippocampus in 3 cats and no eletrophysio-logical, clinical or pathological change was observed in these control study.

In KA group epileptic seizure started with limbic status and developed into generalized status. The course may be divided in 3 stages.

1) Limbic status stage

Immediately after injection of KA, focal multiple spiking discharges on EEG started in the injected hippocampus and propagated into bilateral limbic system with clinical manifestations of limbic seizure such as attention, immobility and couching. Clinically cats started to run around the opposite side of the injection and finally became unable to keep standing and lay down with continuing walking like movement in four limbs. Autonomic signs such as hypersalivation, mydriasis and hyperventilation were also observed. These limbic seizures continued for 2-3 days clinically as well as on EEG.

2) Transfer stage

Two to three days after injection, cats became free of seizures and restored thier activities, though sporadic and synchronous spikes were still observed in the limbic system. Thereafter a secondary epi-leptogenic focus developed on EEG in the ipsilateral amygdala followed by repeated amygdaloid seizures manifested with licking, chewing, head nodding and ipsilateral facial twitching. Day by day the amygdaloid seizure increased in frequency and intensity.

3) Generalized status stage

About 10 days after injection, a secondary gener-alized seizure started. Electroencephalographically the hippocampal spikes of the injected side trig-gered successive multiple spikes in the ipsilateral amygdala and other limbic structures and finally resulted in generalized convulsion. Clinically cats exhibited generalized status epilepticus and died of cachexia about 20 days after injection.

Histological study disclosed an extensive cell loss of pyramidal cell layer in the hippocampus of the injected side.

There are two characteristics in this new model of epilepsy. One is the prolonged epileptic dis-charges in the hippocampus of the injected side, which started immediately after injection and continued until death. Another feature is develop-ment of seizure in 3 stages from limbic stage to generalized status stage with an intermission; transfer stage.

The mechanism in the generalization of limbic status in our model is interesting in understanding a clinical generalization of focal epilepsy. We pos-tulate that the formation of the secondary epilep-togenic focus in the ipsilateral amygdala by per-sistent bonbardments on the spike discharges from the injected hippocampus plays an important role.

We conclude that this model of epilepsy is a good one to investigate a secondary epileptogenic focus and the process of generalization from limbic seizure.

Copyright © 1981, Igaku-Shoin Ltd. All rights reserved.


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