Anti-inflammatory drugs in epilepsy: does it impact epileptogenesis?

Abstract

Introduction: In the epilepsy therapeutic arena, there is urgent need for developing novel antiepileptogenesis treatments that offer a way to prevent the onset or the progression of the disease. Such treatments are still lacking, and their development requires a deep understanding of the mechanisms underlying the disease pathogenesis, in order to target them using appropriate drugs with timely interventions.

Areas covered: Preclinical research highlighted glial cells in seizure-prone areas as key contributors to neuronal circuit hyperexcitability resulting in seizures. Microglia and astrocytes activated by epileptogenic insults increase their synthesis and release of pro-inflammatory molecules, thus contributing to the generation of neuroinflammation. This is now considered an established hallmark of epileptogenic foci in various forms of pharmaco-resistant epilepsies. Studies done in experimental models of non-genetic forms of epilepsy demonstrated that specific inflammatory molecules are involved in seizures, cell loss and co-morbidities.

Expert opinion: Emerging findings highlight that specific inflammatory molecules are potential targets for drug intervention for preventing or arresting epileptogenesis. These drugs, by interfering with mechanisms implicated in disease development, may represent disease-modifying treatments. Clinical translation of anti-inflammatory intervention may take advantage of drugs already used in clinical practice for peripheral or other CNS disorders with a pathogenic neuroinflammatory component.

Keywords: animal models of epilepsy; disease-modification; glia; neuroinflammation; neuronal cell loss; pharmaco-resistant epilepsy.