Abstracts

Direct open- and closed-loop electrical stimulation of the epileptogenic zone has recently been proposed as a potential novel treatment modality for intractable epilepsy. In this study I used bicuculline treated neocortical brain slices to examine on the one hand the efficacy of different electrical stimulation paradigms in preventing and prematurely terminating inter-ictal like epileptiform discharges and seizure-like events, and on the other hand study the cellular mechanisms underlying the antiepileptic effect of cortical electrical stimulation. The study was performed on rat neocortical brain slices treated with the GABA-A receptor blocker bicucculine (BCC, 10 [mu]M). Intracellular voltage recordings were performed using whole-cell recordings from single pyramidal neurons. Extra-cellular recordings from a population of neurons were performed using glass pipettes placed in different regions of the slice. Electrical stimulation was performed using a computer controlled extra-cellular stimulator and either a pipette filled with ACSF or a platinum iridium metal electrode. Bicucculin treated neocortical brain slices produced both inter-ictal like discharges and seizure-like events. Continues recurrent electrical stimulation at frequencies of 0.3-2 Hz eliminated both spontaneous and evoked inter-ictal like discharges and seizure-like events. This effect was dependent on the stimulus intensity and the distance between the origin of the epileptiform discharges and the location of the stimulating electrode. In addition short trains of high frequency electrical stimulation (50-100 Hz, 0.5-2 second-long) terminated 40[plusmn]12 % of seizures. To investigate possible mechanisms underlying the antiepileptic effect of electrical stimulation, I examined its effect on excitatory synaptic transmission and on action potential firing. Both short trains of high frequency stimulation and recurrent low frequency electrical stimulation resulted in a significant reduction of the EPSP amplitude in a frequency dependent manner. High frequency stimulation also decreased the excitability of neurons, and impaired their ability to fire high frequency action potentials. Both recurrent low frequency electrical stimulation and short hig frequency electrical stimulation has an antiepileptic effect in bicuculline treated neocortical brain slices [italic]in-vitro[/italic]. This effect is probably mediated, at least in part, by stimulus evoked depression of excitatory synaptic transmission, in the case of high frequency stimulation decreased excitability of neurons. Further studies are required to examine the antiepileptic effect of electrical stimulation in animal models and humans [italic]in-vivo[/italic]. (Supported by The Chutick foundation)