The Role of Astroglia in the Epileptic Brain

Gabriele Losi, Mario Cammarota, Giorgio Carmignoto

Epilepsies comprise a family of multifactorial neurological disorders that affect at least 50 million people worldwide. Despite a long history of neurobiological and clinical studies the mechanisms that lead the brain network to a hyperexcitable state and to the intense, massive neuronal discharges reflecting a seizure episode are only partially defined. Most epilepsies of genetic origin are related to mutations in ionic channels that cause neuronal hyperexcitability. However, idiopathic epilepsies of unclear origin represent the majority of these brain disorders. A large body of evidence suggests that in the epileptic brain neurons are not the only players. Indeed, the glial cell astrocyte is known to be morphologically and functionally altered in different types of epilepsy. Although it is unclear whether these astrocyte dysfunctions can have a causative role in epileptogenesis, the hypothesis that astrocytes contribute to epileptiform activities recently received a considerable experimental support. Notably, currently used antiepileptic drugs, that act mainly on neuronal ion channels, are ineffective in a large group of patients. Clarifying astrocyte functions in the epileptic brain tissue could unveil astrocytes as novel therapeutic targets. In this review we present first a short overview on the role of astrocytes in the epileptic brain starting from the "historical" observations on their fundamental modulation of brain homeostasis, such as the control of water content, ionic equilibrium, and neurotransmitters concentrations. We then focus our review on most recent studies that hint at a distinct contribution of these cells in the generation of focal epileptiform activities.