Chapter 10 - Inflammation and epilepsy

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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.

Section snippets

Clinical evidence

Clinical evidence supporting a role for inflammation in tissue epileptogenicity stems from three main findings. (1) Various markers of inflammation have been measured in epileptogenic tissue from surgically treated pharmacoresistant patients, namely in malformations of cortical development (ganglioglioma, neuroepithelial tumors, focal cortical dysplasia, tuberous sclerosis) (Maldonado et al., 2003, Ravizza et al., 2006a, Boer et al., 2008), in temporal lobe epilepsy with hippocampal sclerosis (

Experimental studies

The experimental studies addressed three main questions related to: (1) the causes of brain inflammation with a special focus on the involvement of seizures, cell death, or their association as triggering factors; (2) the possibility that a proinflammatory state in the brain can precipitate or predispose to seizures; (3) whether pharmacological or genetic interference with specific inflammatory pathways in the brain can modify seizure frequency or duration, neuronal survival, and

Concluding remarks

The hypothesis that brain inflammation is a significant contributor to seizures and their detrimental consequences, such as neuronal cell loss and BBB damage, is strongly supported by experimental findings and corroborated by clinical observations. Recent findings suggest that chronic inflammation may also contribute to epileptogenesis, thus predisposing the brain to the development of recurrent seizures. Ravizza et al., 2011 Importantly, several inflammatory mediators act as transcriptional

Acknowledgments

The authors thank all colleagues who collaborated with them to originate some of the data described in this chapter, in particular Dr. T.Z. Baram, Dr. E. Aronica, Dr. T. Bartfai, Dr. S.L. Moshé, Dr. B. Viviani, and Dr. M.G. De Simoni. They also thank their sources of support: Dana Foundation, Negri-Weizmann Foundation, Epicure (LSH-CT-2006-037315).

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