Astrocytic Changes Associated with Epileptic Seizures

Abstract

Throughout the central nervous system (CNS), most neurons are closely surrounded by astrocytes. In electron microscopic sections, astrocytes appear to encapsulate neuronal cell bodies and astrocytic processes reach close into the vicinity of synapses. This anatomical proximity gives astrocytes privileged access to the neuronal microenvironment and it is believed that astrocytes actively regulate the extracellular space surrounding neurons. Such regulation appears essential to ensure normal neuronal excitability, since even small changes in extracellular potassium (K⁺), pH, or the accumulation of neurotransmitters can alter or compromise neuronal function. For example, recordings from hippocampal brain slices showed that modest elevations of extracellular K⁺ results in hyperexcitability of hippocampal neurons (1), demonstrating properties that are reminiscent of epileptic seizures. Similarly, compromised astrocytic glutamate uptake, as observed for example in mice lacking astrocytic glutamate transporters, induces epileptic seizures in vivo ⁽²⁾. Thus, fine control of the microenvironment is essential for the maintenance of normal neuronal signaling. To accomplish this role, astrocytes express a number of transport systems, ion channels, and neurotransmitter receptors that are believed to jointly participate in the fine tuning of the neuronal microenvironment (for review, 3–11).