Repetitive transcranial magnetic stimulations of the rat effect of acute and chronic stimulations on pentylenetetrazole-induced clonic seizures

Abstract 

Repetitive transcranial magnetic stimulation (RTMS) has been reported to induce epileptic seizures in normal control and in epileptic patients. Therefore we characterized the effect of acute or chronic stimulations with RTMS on the induction of pentylenetetrazole (PTZ)-induced clonic seizures in the rat. Male Wistar rats were stimulated with a 13-cm coil with a stimulus frequency of 50 Hz. The motor threshold (T_m) was determined by a single transcranial stimulus. Acute stimulation was performed with a stimulus intensity of 0.9 × T_m and 1.5 × T_m using a duration of the train of stimuli of five seconds. Chronic stimulation was performed with a duration of the train of stimuli of one and five seconds using a stimulus intensity of 1.8 × T_m, every day for 30 days. Time to onset of PTZ-induced clonic seizure was determined after the acute stimulation or the last stimulation in chronic RTMS.

In the groups of rats receiving acute RTMS (0.9 and 1.5 × T_m) no seizures developed. No differences were observed in time to onset of clonic seizures after PTZ injection compared to control rats. In the group of rats receiving chronic RTMS some rats showed facial contractions, chewing or head movements during or immediately after the stimulations. None of the rats developed tonic or clonic seizures in relation to RTMS. Time to onset of PTZ clonic seizures was reduced in both groups receiving RTMS with a stimulus duration of one (P < 0.01) and five (P < 0.05) seconds compared to control rats.

The results from this study suggest that acute suprathreshold stimulation with a stimulus frequency of 50 Hz does not affect the induction of clonic PTZ seizures, whereas chronic (daily) stimulations have a facilitatory effect. This indicates that chronic stimulation with RTMS may induce a kindling process in the rat. Chronic RTMS stimulation may therefore represent an interesting alternative non-invasively kindling model to chemical and electrical stimulations.

Keywords:  Repetitive transcranial magnetic stimulation, Kindling, Motor evoked potential, Pentylenetetrazole

Abbreviations:  EMG, Electromyography, RTMS, Repetitive transcranial magnetic stimulation, PTZ, Pentylenetetrazole, ΔT, Time from onset of the infusion to onset of a clear clonic contraction in the forelimbs, T_m, Motor threshold, emg recorded, T_m (VC), Motor threshold, visible contraction

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