Astrocyte dysfunction in epilepsy

Epilepsy comprises a group of disorders characterized by the periodic occurrence of seizures. Currently available anticonvulsant drugs and therapies are insufficient to controlling seizure activity in about one third of epilepsy patients. Thus, there is an urgent need for new therapies that prevent the genesis of the disorder and improve seizure control in individuals already afflicted. The vast majority of epileptic cases are of idiopathic origin, and a deeper understanding of the cellular basis of hyperactivity and synchronization is essential. Neurosurgical specimens from patients with temporal lobe epilepsy typically demonstrate marked reactive gliosis. Since recent studies have implicated astrocytes in important physiological roles in the CNS, such as synchronization of neuronal firing, it is plausible that they may also have a role in seizure generation or seizure spread. In support of this view, several membrane channels, receptors and transporters in the astrocytic membrane have been found to be deeply altered in the epileptic brain, and they are now gradually emerging as new potential targets for antiepileptic therapeutic strategies. This review summarizes current evidence regarding astroglial dysfunction in epilepsy and discusses presumed underlying mechanisms.