A KINDLING MODEL OF PHARMACORESISTANT TEMPORAL LOBE EPILEPSY IN SD RATS INDUCED BY CORIARIA LACTONE AND ITS POSSIBLE MECHANISM
Abstract number :
1.089
Submission category :
Year :
2002
Submission ID :
3460
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Ying Wang, Dong Zhou, HuaiSu Li, HuiXia Chai, Bing Wang, ShangFu Zhang, Qiao Zhou, Hermann Stefan. Department of Neurology-Epilepsy Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology-Epilepsy Center, Erlangen
RATIONALE: The aim of this study was to develop a new animal kindling model of pharmacoresistant temporal lobe epilepsy (TLE) by intramuscular injection of coriaria lactone (CL), and explore the mechanisms that might be involved.
METHODS: Healthy male Sprague-Dawley rats (n=160) were randomized into six groups: three groups (n=50 for each group) received CL injection at subthreshold dosages (1.25mg/kg, 1.5mg/kg and 1.75mg/kg, respectively) and ten received normal saline (NS) injection as control group. The maximal human adult dosage of carbamazepine, valproate and phenytoin was administered as monotherapy to different groups of kindled rats for one month. Changes in electroencephalographic recording, seizure number, intensity and duration including spontaneous seizures during different interventions were compared. The expression of P-170, a multiple drug resistance gene (MDR1) encoding P-glycoprotein, was measured in brain samples from different groups of experimental rats.
RESULTS: A total of 70 (46.7%) rats were fully kindled with a median of 15 CL (seven[mdash]20) injections. ECoG and EHG monitoring revealed the hippocampal origins of epileptiform potentials, which were consistent with the behavior changes observed. Spontaneous seizure occurred with similar frequency and diurnal pattern to human TLE. The antiepileptic drugs tested were ineffective for seizure control. The maximal P-170 expression was in the kindled rats with antiepileptic drugs (AEDs) treatment, the next highest was in the kindled rats without AED intervention. Non-kindled SD rats with CL injection also had increased P-170 expression compared to control SD rats.
CONCLUSIONS: The study provided a simple and stable animal TLE kindling model with pharmacoresistant properties. The pharmacoresistance to carbamazepine, valproate and phenytoin observed in the kindled rats together with the increased P-170 expression was a distinct feature of this model. This model might be used in further investigations of the mechanisms involved in pharmacoresistant TLE and for developing new AEDs.