title: Experimental studies in epilepsy: immunologic and inflammatory mechanisms.
abstract: In this article, we review the literature based on experimental studies lending credence to a relationship between epilepsy and immune-mediated mechanisms linked to central nervous system innate immunity. The brain innate immunity responses to neuronal injury or excessive neuronal activity are mediated by resident microglia and astroglia, but also neurons play an immunomodulatory role. Antigens or antibodies applied to the brain trigger an epileptogenic and inflammatory response. Furthermore, seizure activity and status epilepticus elicit the production and release of proinflammatory cytokines and chemokines. The immune pathogenesis of epilepsy involves complex cell-to-cell interactions including a cross talk between astrocytes and neurons, between astrocytes and brain microvascular endothelial cells, as well as reciprocal leukocyte-endothelial interactions in the context of disruption of the blood-brain barrier. There is a large body of literature from experimental studies showing that seizures can initiate a cascade of innate and adaptive immune responses from various cellular sources and perpetuate neuroinflammation through mechanisms involving transcription of inflammatory genes or posttranslational changes in cytokine release machinery. These inflammatory processes could also possibly contribute to the pathogenesis of comorbidities often associated with epilepsy. This opens exciting possibilities for the development of disease-modifying drugs aimed at mitigating neuroinflammation as a means of ameliorating epileptogenesis and lessening or preventing postictal brain injury.
authors.affiliation: Section of Neurology, St. Christopher's Hospital for Children, Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA. Electronic address: alegido@drexelmed.edu.
authors.forename: Agustín
authors.initials: A
authors.lastname: Legido
authors.affiliation: Section of Neurology, St. Christopher's Hospital for Children, Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA.
authors.forename: Christos D
authors.initials: CD
authors.lastname: Katsetos
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004660:Encephalitis / Q000209:etiology*; D004827:Epilepsy / Q000150:complications / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate