Chaotic electrical stimulation of the subthalamic nucleus – mossy fiber sprouting, epileptic seizures, and brain electrical activity in pentylenetetrazol-kindled rats

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Abstract

BACKGROUND:

Previous studies have demonstrated that appropriate interventions can alter brain electrical activity of epileptic patients prior to and during a seizure, leading to maintenance of a highly chaotic state, thereby inhibiting abnormal epileptic discharges, and eventually controlling epileptic seizure.

OBJECTIVE:

This study was designed to observe the effects of chaotic electrical stimulation to the subthalamic nucleus on mossy fiber sprouting, epileptic seizures, and electrical discharges, and to summarize the most suitable intervention.

DESIGN, TIME AND SETTING:

This randomized grouping, neuroelectrophysiological study was performed at the Laboratory of Neurology, Union Hospital Affiliated to Fujian Medical University in September 2007.

MATERIALS:

Fifty-five healthy, male, Sprague Dawley rats were subjected to an epileptic model by an intraperitoneal injection of pentylenetetrazol. The YC–2 programmed electrical stimulator was provided by Chengdu Instrument Factory, China; the video electroencephalographic system (KT–88–2400) and 24-hour active electroencephalographic system were products of Contec Medical System Co., Ltd., China; pentylenetetrazol was purchased from Sigma, USA.

METHODS:

The present interventional method consisted of electrical stimulation to the subthalamic nucleus with an intensity of 500 μA, pulse width 0.05 ms, frequency 30 Hz, and a duration of 20 minutes for 14 successive days. Fifty-five rats were divided into 6 groups: (1) pre-stimulation (n = 10), pentylenetetrazol was administered and 30 minutes later, chaotic electrical stimulation was performed; (2) synchronous stimulation (n = 10), rats received pentylenetetrazol and chaotic electrical stimulation concurrently; (3) post-administration stimulation (n = 10), after pentylenetetrazol administration, chaotic electrical stimulation was performed immediately after cessation of a seizure; (4) sham-stimulation (n = 10), following pentylenetetrazol administration, an electrode was connected to the stimulator, but electrical stimulation was not performed; (5) control (n = 10), pentylenetetrazol administration, but no electrode was implanted; (6) blank control (n = 50), administration of the same amount of physiological saline and chaotic electrical stimulation.

MAIN OUTCOME MEASURES:

Timm-stained granule change was scored. Simultaneously, electroencephalography was performed to acquire seizure counts and time course of epileptic discharge within 24 hours.

RESULTS:

Timm scores were lower in the electrically stimulated rats than in the non-stimulated rats (P < 0.01). Timm scores were lowest in the synchronous stimulation group. When the rats suffered from tonic clonic seizure, the electroencephalogram primarily showed a persistent spike-slow wave and sharp wave. For the electrically stimulated rats, the mean values of seizure counts and time course of epileptic discharge during each hour were noticeably decreased compared with the non-stimulated rats. The synchronous stimulation group, however, had the lowest seizure counts and the shortest time course, followed by the pre-stimulation group, and lastly the post-administration stimulation group. Significant differences existed among the groups (P < 0.01). Compared with the pre-stimulation group and the post-administration stimulation group, the latent period of grades I and IV epileptic seizures was significantly prolonged, and the time course of tonic clonic seizure, as well as total time course, were significantly shortened in the synchronous stimulation group (P < 0.01).

CONCLUSION:

Simultaneous administration of pentylenetetrazol together with chaotic electrical stimulation produced the greatest inhibitory effects on epileptic seizures. This is possibly related to inhibition of abnormal mossy fiber spouting in the hippocampus.

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