Research progress on pathogenesis and treatment of drug-resistant epilepsy / 药学学报

Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.

Modification of 6 Hz corneal kindled mouse model for drug-resistant epilepsy and its treatment by three traditional Chinese medicine prescriptions / 药学学报

Drug-resistance is a challenge in the treatment of epilepsy, and traditional Chinese medicine (TCM) prescription may have a potential in therapy of the epilepsy. Here we established a modified 6 Hz corneal kindled mouse model of epilepsy, and verified its drug-resistance to four commonly used western medicines. We evaluated the efficacy of three classical TCM prescriptions in this drug-resistant epilepsy model. The results showed that:① most C57BL/6J mice with stimulation current intensity at 44 mA (8 out of 10) were fully kindled, while none ICR mice with stimulation current intensity at 44 mA or C57BL/6J mice with stimulation current intensity at 24 mA were fully kindled. Fully kindled mice exhibited epileptic electroencephalograms after 44 mA and 6 Hz corneal kindling stimulation and increased activation of astrocytes in the hippocampus (by staining the glial fibrillary acidic protein); ② 50 mg·kg-1 phenytoin sodium, 100 mg·kg-1 valproic acid sodium and 15 mg·kg-1 lamotrigine had no significant effects on the drug-resistant seizures in 6 Hz corneal kindled C57BL/6J mice, while 100 mg·kg-1 levetiracetam significantly reduced the seizure stage (P P -1) and Tian-Ma Gou-Teng decoction (14.82 or 44.46 g·kg-1), had no significant effects on the drug-resistant seizures in 6 Hz corneal kindled C57BL/6J mice, while TCM prescription Feng-Yin decoction (19.11 g·kg-1) significantly reduced both the seizure stage (P P < 0.05) in it. Thus, the modified 6 Hz corneal kindled C57BL/6J mouse model is an excellent drug-resistant epilepsy model, Feng-Yin decoction have antiepileptic effects on it, suggesting Feng-Yin decoction may be an effective TCM prescription for clinical treatment of drug-resistant epilepsy.