Anti-epileptogenic effect of high-frequency stimulation in the thalamic reticular nucleus on PTZ-induced seizures.

BACKGROUND: Deep brain stimulation, specifically high-frequency stimulation (HFS), is an alternative and promising treatment for intractable epilepsies; however, the optimal targets are still unknown. The thalamic reticular nucleus (TRN) occupies a key position in the modulation of the cortico-thalamic and thalamo-cortical pathways. OBJECTIVE: We determined the efficacy of HFS in the TRN against tonic-clonic generalized seizures (TCGS) and status epilepticus (SE), which were induced by scheduled pentylenetetrazole (PTZ) injections. METHODS: Male Wistar rats were stereotactically implanted and assigned to three experimental groups: Control group, which received only PTZ injections; HFS-TRN group, which received HFS in the left TRN prior to PTZ injections; and HFS-Adj group, which received HFS in the left adjacent nuclei prior to PTZ injections. RESULTS: The HFS-TRN group reported a significant increase in the latency for development of TCGS and SE compared with the HFS-Adj and Control groups (P < 0.009). The number of PTZ-doses required for SE was also significantly increased (P < 0.001). Spectral analysis revealed a significant decrease in the frequency band from 0.5 Hz to 4.5 Hz of the left motor cortex in the HFS-TRN and HFS-Adj groups, compared to the Control group. Conversely, HFS-TRN provoked a significant increase in all frequency bands in the TRN. EEG asynchrony was observed during spike-wave discharges by HFS-TRN. CONCLUSION: These data indicate that HFS-TRN has an anti-epileptogenic effect and is able to modify seizure synchrony and interrupt abnormal EEG recruitment of thalamo-cortical and, indirectly, cortico-thalamic pathways.

[Electrical stimulation of the vagal nerve: from experimental to clinical aspects]. / Estimulación eléctrica del nervio vago: de lo experimental a lo clínico.

INTRODUCTION AND AIMS: This review focuses its attention on the studies that have been conducted to determine the influence of electrical stimulation of the vagal nerve on experimentally induced convulsive activity and its application in the clinical field. The literature published to date describes an anticonvulsive effect on the seizures triggered by pharmacological agents and by electrical stimulation such as electroshock, and in the amygdaline electrical kindling model a delay in the generalisation of the convulsive activity is observed. DEVELOPMENT: The first experimental observations showed that electrical stimulation of the vagal nerve can have effects on EEG activity, including synchronisation and desynchronisation of the electrical activity of the brain, as well as promoting an increase in the amount of REM sleep. These observations served as the basis for the renewed interest in the electrical stimulation of the vagal nerve in experimental models and testing its effectiveness in patients with medication-resistant epilepsy. Nevertheless, the mechanisms accounting for the anticonvulsive effect remain unknown. CONCLUSIONS: These observations open up the possibility of studying the role played by neurotransmitters and neuromodulators in the anticonvulsive process of the electrical stimulation of the vagal nerve in experimental models of epilepsy and offer evidence of its possible action in the human brain.

Vagus nerve prolonged stimulation in cats: effects on epileptogenesis (amygdala electrical kindling): behavioral and electrographic changes.

PURPOSE: To analyze the effect of prolonged (daily) electrical vagus nerve stimulation (VNS) on daily amygdaloid kindling (AK) in freely moving cats. METHODS: Fifteen adult male cats were implanted in both temporal lobe amygdalae, both lateral geniculate bodies, and prefrontal cortices. A bipolar hook (5-mm separation) stainless steel electrode also was implanted in the unsectioned left vagus nerve. AK only was performed on five of the cats as a control. The remaining 10 cats were recorded under the following experimental conditions: VNS (1.2-2.0 mA, 0.5-ms pulses, 30 Hz) for 1 min along with AK (1-s train, 1-ms pulses, 60 Hz, 300-600 microA), followed by VNS alone for 1 min, four times between 11:00 a.m. and 2 p.m. At different times, VNS was arrested, and AK was continued until stage VI kindling was reached. RESULTS: The behavioral changes evoked by VNS were as follows: left miosis, blinking, licking, abdominal contractions, swallowing, and eventually yawning, meowing, upward gaze, and short head movements. Compulsive eating also was present with a variable latency. Outstanding polygraphic changes consisted of augmentation of eye movements and visual evoked potentials while the animal was awake and quiet, with immobility and upward gaze. An increase of the pontogeniculooccipital (PGO) wave density in rapid eye movement (REM) sleep also was noticeable. AK was completed (to stage VI) in the control animals without a vagus nerve implantation in 23.4+/-3.7 trials. In animals with VNS, the AK was significantly delayed, remaining for a long time in the behavioral stages I-III and showing a reduction of afterdischarge duration and frequency. Stage VI was never reached despite 50 AK trials, except when the vagus nerve electrodes were accidentally broken or vagal stimulation was intentionally arrested. Under these circumstances, 24.4+/-8.16 AK trials alone were necessary to reach stage VI of kindling. CONCLUSIONS: Our results indicate that left, electrical VNS interferes with AK epileptogenesis. This anticonvulsant effect could be related to the increase of REM sleep.