RESUMEN
Animal models reproducing the characteristics of human epilepsy are essential for the elucidation of the pathophysiological mechanisms. In epilepsy research there is ongoing debate on whether the epileptogenic process is a continuous process rather than a step function. The aim of this study was to assess progression of epileptogenesis over the long term and to evaluate possible correlations between SE duration and severity with the disease progression in the kainic acid model. Rats received repeated KA injections (5mg/kg) until a self-sustained SE was elicited. Continuous depth EEG recording started before KA injection and continued for 30 weeks. Mean seizure rate progression could be expressed as a sigmoid function and increased from 1 ± 0.2 seizures per day during the second week after SE to 24.4 ± 6.4 seizures per day during week 30. Seizure rate progressed to a plateau phase 122 ± 9 days after SE. However, the individual seizure rate during this plateau phase varied between 14.5 seizures and 48.6 seizures per day. A circadian rhythm in seizure occurrence was observed in all rats. Histological characterization of damage to the dentate gyrus in the KA treated rats confirmed the presence of astrogliosis and aberrant mossy fiber sprouting in the dentate gyrus. This long-term EEG monitoring study confirms that epileptogenesis is a continuous process rather than a step function.
Asunto(s)
Ondas Encefálicas/efectos de los fármacos , Electroencefalografía , Epilepsia del Lóbulo Temporal/inducido químicamente , Agonistas de Aminoácidos Excitadores/toxicidad , Ácido Kaínico/toxicidad , Análisis de Varianza , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Ritmo Circadiano/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Monitoreo Fisiológico , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: In many temporal lobe epilepsy (TLE) patients both hippocampi are seizure onset zones. These patients are unsuitable candidates for epilepsy surgery but may be amenable to hippocampal deep brain stimulation (DBS). The optimal DBS parameters for these patients are unknown. Recent observations suggest that even in patients with a unilateral focus switching from unilateral hippocampal DBS to bilateral hippocampal DBS could improve seizure control. OBJECTIVE: Compare the effect of unilateral with bilateral hippocampal DBS on seizures in a rat model for TLE. METHODS: In the post status epilepticus (SE) kainic acid rat model for TLE continuous EEG monitoring was performed for 50 days during which rats were subjected to 10 days of unilateral and 10 days of bilateral Poisson-distributed high frequency hippocampal DBS in a cross-over trial. During bilateral DBS, each hippocampus was stimulated with a separate stimulator and its own generated Poisson distribution with a mean and variance of 1/130 s. RESULTS: Electrographic seizure rate was 23% lower during bilateral compared to unilateral hippocampal DBS (P < 0.05). No effect of unilateral nor bilateral hippocampal DBS was observed on seizure duration. When bilateral hippocampal DBS was applied, lower stimulation intensities were required to evoke after discharges (P < 0.05), reflecting a higher potency of bilateral hippocampal DBS compared to unilateral hippocampal DBS to affect hippocampal networks. CONCLUSIONS: Superior outcome in seizure control with bilateral compared to unilateral hippocampal DBS indicates that targeting larger regions of the hippocampal formation with more than one stimulation electrode may be more successful in suppressing seizures in TLE.