RESUMO
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.
Assuntos
Estimulação Encefálica Profunda , Convulsões/fisiopatologia , Convulsões/terapia , Núcleos Talâmicos/fisiopatologia , Animais , Córtex Cerebral/fisiopatologia , Masculino , Pentilenotetrazol , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Estado Epiléptico/fisiopatologia , Estado Epiléptico/terapiaRESUMO
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.
Assuntos
Comportamento Animal/fisiologia , Eletroencefalografia , Epilepsia/etiologia , Excitação Neurológica/fisiologia , Lobo Temporal/fisiopatologia , Nervo Vago/fisiologia , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/fisiopatologia , Animais , Gatos , Estimulação Elétrica , Epilepsia/fisiopatologia , Masculino , Polissonografia , Sono REM/fisiologia , Lobo Temporal/fisiologiaRESUMO
The effect of amygdaloid kindling on sleep organization was tested in chronically implanted cats on a 12:12 light-dark cycle. Electrical kindling stimuli were delivered to the amygdala every 2 h during the light period. Total sleep time and percentage, mean duration, and mean number, as well as the hourly accumulation of waking (W) and sleep (slow wave sleep I and II, and paradoxical sleep) episodes were assessed from daily 23-h sleep recordings, consisting of baseline control recordings, control recordings where cats were briefly alerted at 2-h intervals to mimic the kindling trials manipulation, and recordings on each kindling day. The kindling process was completed within six days achieving three to five consecutive fully kindled seizures. Analysis of total recording time showed that the kindling process enhanced W stage and diminished total sleep time only on the second kindling day. Analysis of light and dark periods demonstrated compensatory W and sleep changes during the dark periods. Hourly sleep stage time accumulation was slowed during kindling trials, but compensated while stimuli were suspended. All of these changes returned to baseline values at the end of kindling. No significant differences between changes induced by kindling and those produced by alerting trials were found. We conclude that sleep alterations can not be exclusively attributed to kindling development, and that sleep is able to become adapted to the focal and generalized seizures effect.