Overview Article Astrocytes as Initiators of Epilepsy

Astrocytes play a dual role in the brain. On the one hand, they are active signaling partners of neurons and can for instance control synaptic transmission and its plasticity. On the other hand, they fulfill various homeostatic functions such as clearance of glutamate and K⁺ released from neurons. The latter is for instance important for limiting neuronal excitability. Therefore, an impairment or failure of glutamate and K⁺ clearance will lead to increased neuronal excitability, which could trigger or aggravate brain diseases such as epilepsy, in which neuronal hyperexcitability plays a role. Experimental data indicate that astrocytes could have such a causal role in epilepsy, but the role of astrocytes as initiators of epilepsy and the relevant mechanisms are under debate. In this overview, we will discuss the potential mechanisms with focus on K⁺ clearance, glutamate uptake and homoeostasis and related mechanisms, and the evidence for their causative role in epilepsy.