Inflammation includes a variety of protective processes that have evolved to activate a defensive attack against noxious stimuli, thus representing an important endogenous homeostatic mechanism of the organism. Usually, the outcome of the inflammatory program is a rapid repair of tissue damage; however, if these processes are not properly controlled in timing and extent, then inflammation becomes deleterious, thus leading to permanent tissue damage and cellular dysfunction, as suggested to occur in chronic neurodegenerative disorders and in epilepsy. This chapter provides a brief overview of the experimental and clinical evidence linking brain inflammation to epilepsy. We describe three groups of inflammatory mediators-namely, cytokines, the complement system, and cyclooxygenase-2 (COX-2). Their expression is increased in rodent and human epileptogenic tissue, such as in temporal lobe epilepsy and malformations of cortical development that do not feature a typical inflammatory pathophysiology. Pharmacological attempts have been made in experimental models to understand their functional role in seizure activity, epileptogenesis, and seizure-induced neuronal cell death. Current knowledge suggests an involvement of these specific inflammatory pathways in the pathogenesis of seizures, thus highlighting new potential therapeutic strategies. In this chapter, we first describe changes in the expression of cytokines, the complement system, and COX-2 in epileptogenic tissue of experimental models and humans. We next discuss the pharmacological data addressing the functional consequences of brain expression of these inflammatory mediators on seizures, epileptogenesis, and cell loss. Finally, recent evidence describing the mechanisms by which brain inflammation can alter neuronal circuit excitability and seizure activity is reported.
|Title of host publication||Epilepsy|
|Subtitle of host publication||Mechanisms, Models, and Translational Perspectives|
|Number of pages||15|
|Publication status||Published - 1 Jan 2010|