Objectives The purpose of this study is to verify the phenytoin-resistant mesial temporal lobe epilepsy (MTLE) induced by Li-pilocarpine and screened by antiepilepsy drug (AEDs). Methods The rats with MTLE were induced by Li-pilocarpine, which were screened by effect of phenytoin treatment monitored by vedio-EEG. The living microdialysis technology was used for verification of drug concentration in brain of drug-resistant and drug-responsive rat model, and the P-glycoprotein expression was detected by immunohistochemical method. Results Sixteen rats with chronic MTLE were successfully induced in total 30 rats, among which, 6 drug-resistant rats with MTLE were screened. The brain/plasma ratio of area under the curve in drug-resistant rats was significantly lower than that of drug-responsive rats (0.15±0.03 vs. 0.28±0.05, P<0.05). In addition, the P-glycoprotein expression in brain of drug-responsive rats was obviously higher than that of drug-responsive rats (P<0.05). Conclusions The low concentration of phenytoin in drug-resistant rat model with MTLE was verified that might be related to the over-expressed P-glycoprotein in brain.
ObjectiveIn order to evaluate that whether the P-glycoprotein-inhibitor verapamil (VPM) could effect the distribution of antiepileptic drug phenytoin (PHT) in a rat model of mesial temporal lobe epilepsy (MTLE).MethodsThe rat models of MTLE were induced by li-pilocarpine and were randomly divided into two groups (PHT group and VPM+PHT treatment group) to compare the PHT distribution in brain, liver and kidney. Brain dialysate samples were collected by microdialysis technology. And the analysis of samples for PHT concentration was performed by high performance liquid chromatography (HPLC). The comparisons were carried out by t test (or Wilcoxon test).ResultsIn VPM+PHT treatment group, 4 out of 9 rats were dead within 30 minutes after drug administration. The significantly decreased area under the curve (AUC) ratio of brain/plasma in VPM+PHT group was 0.11±0.06 when compared with PHT group 0.21±0.02 (t=3.237, P=0.025), while there were no significant differences in ratios of liver/plasma ［PHT (1.12±0.37) vs. VPM+PHT (0.99±0.27), Z=−0.490, P=0.624］ and kidney/plasma ［PHT (0.74±0.16) vs. VPM+PHT (0.49±0.26), t=1.872, P=0.103］ between two groups.ConclusionsThe P-glycoprotein-inhibitor VPM significantly decreased PHT level in brain of rat with MTLE.
ObjectTo investigate the pathogenesis of drug-resistant epilepsy by examining the expression of mRNA and protein of Cell Division Cycle 42 GTP-binding protein (Cdc42), Neural Wiskott-Aldrich Syndrome Protein (N-WASP) and Actin-related protein 2/3(Arp2/3) in peripheral blood of patients with drug-resistant epilepsy (DRE).MethodsSeventy two essential epilepsy patients who were attended at outpatients and inpatients in the Department of Neurology of the Affiliated Hospital of Youjiang Medical University for Nationalities were selected from October 2016 to October 2018. According to the 2010 International League Against Epilepsy’s definition of Drug-Resistant Epilepsy, the patients were divided into 2 groups: 32 patients with DRE were defined as DRE group, 40 patients with anti-epilepsy drugs (AEDs) well controlled were defined as the well controlled group. Thirty two healthy persons were selected as control group. The expression of mRNA and protein of Cdc42, N-WASP and Arp2/3 in peripheral blood were measured by quantitative real-time PCR (RT-qPCR) and Western blot(WB). Experimental data were analyzed by ANOVA or rank-sum test.ResultsCompared with well-controlled group and healthy persons group, Cdc42, N-WASP, Arp2/3 in DRE group were significantly increased, the differences were statistically significant (P<0.05). Compared with the control group, Cdc42, N-WASP, Arp2/3 in well-controlled group were significantly increased, with statistically significant differences (P<0.05).ConclusionThe expression of Cdc42, N-WASP, Arp2/3 in peripheral blood of patients with DRE significantly increased, being closely related to the occurrence and development of DRE, and used as indicators in peripheral blood predicting the occurrence of DRE.
Approximately 70 million people worldwide suffer from epilepsy, with about 9 million in China. About one-third of patients demonstrating resistance to traditional antiseizure medications (ASMs), Focal Cortical Stimulation (FCS) emerges as a novel neuromodulation therapy based on neural stimulation, showing potential in treating drug-resistant focal epilepsy. FCS reduces seizure frequency by diminishing abnormal excitability in cortical areas. Compared to traditional surgery, it carries lower risks and is particularly suited for patients whose epileptogenic foci are difficult to surgically localize. Its adjustability provides physicians with treatment flexibility, allowing them to tailor therapy based on patient conditions. Recent studies highlight the practical clinical application of FCS, underscoring its advantages in reducing the frequency of drug-resistant epilepsy seizures. The article concludes by exploring the future prospects of FCS, emphasizing the need for research in long-term efficacy assessment and patient adaptability, thus demonstrating its significant potential and direction for development in the field of epilepsy treatment.