Neuroglia in epilepsy

Epilepsy is a group of neurologic diseases characterized by spontaneous, repetitive disruption to neuronal activity. Neurons have been at the core of epilepsy research efforts, and pharmacotherapies historically have been generated by targeting neuronal mechanisms. As a result, most currently available antiseizure drugs (ASDs) work to either decrease excitatory glutamatergic neurotransmission or to increase inhibitory GABAergic neurotransmission. However, ASDs may have undesirable side effects on cognition and also fail to control seizures in approximately 30% of epilepsy patients. In recent years, glia have surfaced as essential modulators of neuronal function in health and disease. The redirection of focus onto neuroglia provides new perspectives and opportunities to generate novel therapeutic targets that may treat refractory epilepsy and diminish the unwanted side effect profile of current treatments. In this chapter, we discuss the contribution of astroglia, oligodendroglia, and microglia to the genesis, development, and progression of epilepsy, and we highlight key enzymes, receptors, transporters, and channels that may be pursued as nonneuronal targets for novel ASDs.