Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Drug-induced seizure is one of the serious adverse effects of neurotoxicity for drug development. In preclinical studies, seizure is usually evaluated by in vivo toxicity studies, but there are many efforts for seizure evaluation because of continuous observation including nocturn periods. In addition, it is difficult to judge whether abnormal signs lead to seizure.
Electroencephalogram (EEG) can directly and temporally detect the neuronal activity, and abnormal waveforms during seizure condition have been reported in the animal studies. Therefore, EEG is the useful tool for detecting seizure. However, EEG has not been used as a biomarker for seizure prediction since there are few reports on an evaluation of seizure potential at doses that do not occur to seizure. Therefore, we establish a novel analytical method detecting seizure potential using by EEG.
EEG data was obtained after administration of several seizure-inducing compounds to rats at doses that do not occur to seizure. Ten parameters were calculated from each frequency of the EEG data, and the multivariate analysis was performed. As the result, the multivariate analysis was revealed to the seizure potential of the seizure-inducing compounds. These results indicate that EEG analysis in rats is a useful tool to clear seizure potential.
We are also investigated the relationship between cerebrospinal fluid concentrations of each compound and the concentrations to judge as seizure condition in in vitro microelectrode array (MEA) system. Moreover, we indicate the evaluation flow of seizure potential using EEG and MEA.
