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The therapeutic management of epilepsies is often challenging with up to 30% of patients suffering from drug-resistant seizures. Elucidation of the mechanisms of drug resistance can guide future development of optimized therapeutic strategies. Therapeutic failure can be related to disease-associated alterations in targets and in brain penetration rates of antiepileptic drugs. Studies in rodent models and in freshly isolated human brain capillaries helped to identify the signaling mechanisms contributing to altered blood-brain barrier function in the epileptic brain. The findings suggest novel targets to overcome drug resistance and imaging biomarkers for prediction of drug-responsiveness based on positron emission tomography.
A gain in knowledge about the pathophysiological mechanisms of epilepsy development following epileptogenic brain insults renders a basis for the development of preventive strategies. However, our understanding of the complex molecular and cellular alterations resulting in the formation of a hyperexcitable epileptic network is still incomplete. Differential proteome analysis during epileptogenesis renders comprehensive information about the time course and patterns of molecular events. The analysis of these comprehensive data sets guides the selection of future target candidates and molecular biomarkers for antiepileptogenic approaches.