Cell culture models for epilepsy research and treatment

Abstract

Acquired or hereditary epilepsy affects millions of people. Today, the disease is pharmacoresistant in about 30 percent of cases, meaning that the seizures do not come under acceptable control in response to medication. Therefore, there is a great need for the development of novel methods for epilepsy research and treatment. Although in vivo animal models best mimic the clinical features of epilepsy, in vitro models have clear advantages in elucidating the fine details and cellular mechanisms of neurological disorders. In contrast to short-lived experiments in acute brain slices, cell cultures are often chosen as chronic models for antiseizure medication screening and epilepsy research under reduced, well-controlled in vitro conditions that still include all major cell types susceptible to epileptic seizures. Organotypic brain slices or dissociated cells produce spontaneous synchronized epileptiform discharges classified as interictal and ictal-like. In addition, pharmacologically or electrically induced seizures and status epilepticus can be obtained for electrophysiological and imaging experiments. Relatively simple cell cultures of primary rodent neurons provide entry-level models for the initial screening of antiseizure medications and basic epilepsy research. However, more sophisticated human cultures of stem cell-derived neurons offer the possibility of medical studies using the human genotype without the need to obtain brain tissue from patients. As an evolution of this method, programmed differentiation of brain cells is now being used in stem cell therapy for neurological disorders. Overall, cell culture greatly expands the repertoire of methods available to study epileptic disorders and potential cures.