A Kindling Model of Pharmacoresistant Temporal Lobe Epilepsy in Sprague–Dawley Rats Induced by Coriaria Lactone and Its Possible Mechanism

作者：Ying Wang, Dong Zhou, Bing Wang, Huaisu Li, H Chai, Qiao Zhou, Shangfu Zhang, Hermann Stefan · 发表于：Epilepsia · 年份：2003 · DOI：10.1046/j.1528-1157.2003.32502.x · 被引用次数：55 · 研究领域：Biological and pharmacological studies of plants、Plant-based Medicinal Research、Medicinal Plants and Bioactive Compounds

PURPOSE: The aim of this study was to develop a new animal model of pharmacoresistant temporal lobe epilepsy (TLE) by repeated intramuscular injection of Coriaria lactone (CL) at subthreshold dosages and to explore the mechanisms that might be involved. METHODS: Healthy male Sprague-Dawley rats (n = 160) were randomized into four groups during the kindling process: three groups (n = 50 for each group) received CL injection at subthreshold dosages (1.25, 1.5, and 1.75 mg/kg, respectively), and ten received normal saline (NS) injection as a control group. The maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) was administered as monotherapy to different groups of kindled rats for 1 month (n = 20 for each group). Changes in EEG recording, seizure number, intensity (expressed as grade 1-5 according to Racine stage), 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 by using an image analysis and measurement system (ImagePro-Plus 4.0). RESULTS: A total of 70 (46.7%) rats were fully kindled with a median of 15 (seven to 20) CL injections. Electrocorticogram (ECoG) including hippocampal (EHG) monitoring revealed the temporal lobe origins of epileptiform potentials, which were consistent with the behavioral changes observed. Spontaneous seizures o...