Abstracts

About 70% of patients with temporal lobe epilepsy (TLE), the most common type of epilepsy in human adults, are resistant to pharmacological treatment. Epilepsy research lacks of animal models for pharmacoresistant epilepsy. Rat models of TLE in which spontaneous seizures develop after a convulsive status epilepticus are increasingly used. However, to our knowledge, only one previous study has described the individual response to an anticonvulsant drug in such a chronic epilepsy model (Glien et al., Epilepsia, 43; 350-7: 2002). The aim of the present study was to investigate whether - similar to epileptic patients - epileptic rats differ in their individual response to an anticonvulsant drug when the drug is given at doses producing plasma levels within the [quot]therapeutic range[quot].
For this purpose, female Sprague-Dawley rats received a prolonged electrical stimulation in the basolateral amygdala which resulted in the development of a self-sustained status epilepticus. Several weeks after this treatment the rats developed spontaneous recurrent epileptic seizures. For the investigation of the anticonvulsant drug phenobarbital (PB), a combined EEG- and video-monitoring system was used to observe continuously the epileptic rats over a time period of 6 weeks. The 6 week observation period was divided as follows: two weeks predrug-, drug-, and postdrug-phase, respectively. In the predrug- and the postdrug-phase the rats received systemic injections of saline twice daily. In the drug phase the rats received an initial, systemic injection of 25 mg/kg PB followed by systemic injections of 15 mg/kg PB twice daily to maintain a constant plasma level of 10 [ndash] 30 [micro]g/ml. The EEG- and video-monitoring system served to evaluate the seizure frequency, the seizure severity and the seizure duration.
With the application schedule of 15 mg/kg phenobarbital i.p. twice daily a plasma concentration within the therapeutic range could be achieved in all rats. Nevertheless, the epileptic rats differed in their response to phenobarbital. In seven rats the seizure frequency was significantly reduced during the two weeks of phenobarbital treatment (responders) while 4 rats did not respond adequatly to the drug treatment (nonresponders). In the nonresponder group a change in the typ of motor seizures from convulsive to non-convulsive seizures could be noted.
The present data indicate that it is possible to mimic the clinical situation concerning pharmacoresistance to anticonvulsant drug treatment with a rat model of TLE. This rat model might provide a new tool for investigation of the mechanisms underlying pharmacoresistant TLE.