The Role of Astrocytes in Epileptogenesis

Abstract

Epilepsy is a major neurological disorder that affects 0.5-2.0% of the global population (Hauser, 1998; Picot et al.; 2008). The term “epilepsy” likely encompasses a number of various etiological and pathophysiological processes. The International League Against Epilepsy (ILAE) has classified the epilepsies as being either focal or generalized. In all likelihood, this classification implies different causes and anatomical/functional substrates. Epileptogenesis (the processes by which epilepsy develops within an otherwise normal brain) probably differs for the various types of epilepsy (Luders, 2008). In this sense, epileptogenesis of (for example) temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS), would be different from that observed in patients with cortical dysplasia; this would hold true for other cryptogenic or idiopathic focal epilepsies as well. Therefore, to date, it has not been possible to establish a unique underlying cause or mechanism that is involved in the transition from normal to epileptic cortical tissue, although there are several hypotheses to explain the different types of seizures and epilepsies. From a therapeutic point of view, the epilepsies in humans can be divided into pharmaco sensitive and pharmaco resistant. In the former, the patient is successfully treated by one or more anti-epileptic drugs (AED). Nearly two-thirds of patients respond to anticonvulsant therapy. However, in a significant percentage of patients, the seizures cannot be controlled by drugs, despite verifying both maximal dosage and an adequate treatment duration. The percentages of medical intractability among epileptic patients are: focal epilepsy, 24%; idiopathic epilepsy, 9.3%; and catastrophic epilepsy, 66.7% (Lardizabal, 2008). In some cases, a viable therapeutic option is surgery. Generally, the candidates for this treatment are patients who suffer from focal or partial epilepsy. In these patients, it is possible—at least in theory—to identify a well-defined area of the cortex that is responsible for the seizures; this is known as the epileptic zone (EZ). From an operational point of view, the EZ is defined as the region in which excision or disconnection relieves the patient from seizures. This option frequently involves removing the brain section where the EZ is located, and this possibility offers a unique opportunity to gain access to the real processes (the neural networks, membrane properties and synaptic dynamics) underlying partial epilepsy in human patients. TLE is the most common form of partial epilepsy in adults and is usually drug-resistant (Engel 2001; Wieser, 2004). This type of pathology is frequently associated with a salient pathological condition called hippocampal sclerosis (see Figure 1 -Kuzniecky et al.; 1987).