Chapter 10 - Inflammation and epilepsy

Abstract

A role of inflammation in the pathophysiology of human epilepsy has been supported in the last 10 years by varied experimental and clinical evidence. From a clinical standpoint, a role of inflammation in epilepsy had been suggested by the demonstrated antiepileptic activity of selected powerful anti-inflammatory drugs, including steroids, although the mechanistic aspects of the effects of such treatments remained unknown. Inflammatory mediators have been described recently in surgically resected tissue from pharmacoresistant patients with seizures of various etiologies. This observation extends the original view that inflammation is a pathological feature of specific epileptic disorders such as Rasmussen's encephalitis, to the possibility that brain inflammation is indeed a common pathological substrate contributing to tissue epileptogenicity. Experimental studies in models of seizures and epilepsy demonstrated that brain inflammation is not a mere hallmark of tissue pathology but plays an active role in sustaining or precipitating seizures, and contributes to cell loss. The molecular mechanisms by which inflammation may increase tissue excitability are now explored, opening new attractive perspectives for the treatment or prevention of seizures. This chapter reviews the main evidence obtained in epileptic patients and in experimental models of seizures and epilepsy that supports the active involvement of inflammatory processes in tissue hyperexcitability underlying the onset and recurrence of seizures.