Today preclinical epilepsy research is shifting towards the use of true epilepsy models to unravel the processes underlying epileptogenesis. One of the most widely used and thus best characterized animal models for temporal lobe epilepsy is the kainic acid-induced post-status epilepticus rat model. In rodents status epilepticus (SE) is followed by a latent phase during which the brain is rendered epileptic. Eventually the animals develop chronic spontaneous seizures. In order to generate reproducible conditions between rats, the induced SE should be interrupted after 90 minutes. There is consensus that this time interval is sufficient to initiate epileptogenesis and that this approach limits animal suffering. Most research groups use systemic administration of 10 mg/kg diazepam as a standard protocol to interrupt SE. Termination of behavioral seizure activity is currently used by many researchers as sole parameter to monitor the establishment of SE control. Using electrocorticographic (ECoG) monitoring we want to verify whether lack of behavioral seizure activity is indeed always correlated with full SE control. SE was induced in rats by consecutive intraperitoneal kainate injections (5 mg/kg) with a one hour interval. Using simultaneous video-ECoG monitoring establishment of SE was verified behaviorally and electrocorticographically. Diazepam (10 mg/kg) was administered to terminate SE after 90 minutes. SE was controlled in only 28% of the rats after diazepam administration (n=7). Behaviorally, all rats consistently appeared to be seizure free. However this was not confirmed by the ECoG analysis. In 72% of the rats ECoG activity showed continuous epileptic activity despite the lack of typical seizure-related behavioral activity. The present data clearly demonstrate the need to use ECoG monitoring to enable reliable assessment of SE control as the number of false positives is extremely high when SE control is only behaviorally assessed. Our data show that the standard protocol to control SE is not sufficient and needs further optimization.
|Tijdschrift||Acta Neurologica Belgica|
|Status||Published - 2010|