Experimental Seizure Model Induced by Dibutyryl Derivatives of Cyclic Nucleotides
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To investigate the possible roles of cyclic nucleotides in the mechanisms of epi-leptic seizures, dibutyryl-cAMP (db-cAMP) or dibutyryl-cGMP (db-cGMP), either acyclic nucleotide derivative, was injected into the left amygdala of rats in doses of 1.0, 20, 100 and 200μg, and the behavioral and EEG changes were monitored. Afterwards, histological examinations were performed mainly in the dorsal hippo-campus and the injection site (amygdala).<BR>The following results were obtained; 1) Single jerks and sporadic spikes were induced by 1.0 μg of db-cAMP. Facial twitching, searching and sniffing were induced by 20μg of db-cAMP. Seizure development from facial twitching to generalized convulsion was induced by 100μg of db-cAMP, and status epilepticus was induced by 100 big or more of db-cAMP. Very similar seizure patterns were induced by db-cGMP. However, db-cGMP was less potent than db-cAMP for the same dose, and the highest dose of db-cGMP did not cause status epilepticus.<BR>2) At the injection site (amygdala), the histological changes induced by db-cAMP were characterized by neuronal cell losses and gliosis. Similar changes were also produced by db-cGMP.<BR>3) After status epilepticus was induced by db-cAMP, an extensive cell loss in the CA3-4 fields of the pyramidal cell layer was observed in the hippocampus. On the other hand, only minimal changes of the pyramidal cell layer were observed after seizures induced by any dose of db-cGMP and the smaller doses of db-cAMP that did not develop status epilepticus.<BR>4) These results suggest that both db-cAMP and db-cGAMP, in paticular db-cAMP, have neurotoxic and neuroexciting effects similar to those of kainic acid, and that microinjection of these derivatives into the rat amygdala provides a good experimental seizure model for epilepsy and status epilepticus.
- 一般社団法人 日本てんかん学会の論文
一般社団法人 日本てんかん学会 | 論文
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