G.Gamkrelidze
Institute of Chemical Biology, Ilia State University, Tbilisi, Georgia
Epilepsy is one of the most wide spread neurological diseases that currently cannot be cured with drugs. Epileptogenesis is a complex process of molecular, cellular and network changes that transforms a normal brain into an epileptic one. A hallmark of epileptogenesis is a development of pathological hyperexcitability of pyramidal neurons manifested by large paroxysmal depolarizations that are responsible for tonic or rhythmic bursting seizure activity of the neurons. Currently, medically approved therapy that prevents or significantly modifies the process of epileptogenesis does not exist. From this point of view, it is important that our laboratory has recently identified substance myo-inositol (MI) as a potentially very promising antiepileptogenic drug. We hypothesized that one mode of antiepileptic action of MI is to suppress paroxysmal depolarization in pyramidal neurons during epileptogenesis. To test this hypothesis, we utilized two different models of temporal lobe epilepsy epileptogenesis: evoked seizure after discharge in the hippocampus and kainic acid (KA) model. To this end, we implanted electrodes in rat hippocampus, in order to record EEG and stimulate this structure, and investigated MI effects on the duration of seizure after discharge elicited with electrical stimulation in rats untreated with a chemoconvulsant and duration and frequency of spontaneous electrical seizure discharge induced by epileptogenesis in KA treated rats. In addition, in KA treated rats, we studied MI effects on epileptogenesis induced spatial learning and memory decline in water maze test. We have found that MI suppress the generation of evoked seizure after discharge and spontaneous electrographic seizure activity in hippocampus and impedes spatial learning and memory decline induced by epileptogenesis. Obtained results are consistent with our stated hypothesis.