The role of inflammation in epileptogenesis
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REVIEW
Acta Epileptologica
Open Access
The role of inflammation in epileptogenesis Fanwei Meng and Lifen Yao*
Abstract Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life. Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures. Proconvulsant incidences can stimulate immune cells, augment the release of pro-inflammatory cytokines, elicit neuronal excitation as well as blood-brain barrier (BBB) dysfunction, and finally trigger the generation or recurrence of seizures. Understanding the pathogenic roles of inflammatory mediators, including inflammatory cytokines, cells, and BBB, in epileptogenesis will be beneficial for the treatment of epilepsy. In this systematic review, we performed a literature search on the PubMed database using the following keywords: “epilepsy” or “seizures” or “epileptogenesis”, and “immunity” or “inflammation” or “neuroinflammation” or “damage-associated molecular patterns” or “cytokines” or “chemokines” or “adhesion molecules” or “microglia” or “astrocyte” or “blood-brain barrier”. We summarized the classic inflammatory mediators and their pathogenic effects in the pathogenesis of epilepsy, based on the most recent findings from both human and animal model studies. Keywords: Epileptogenesis, Inflammatory mediators, Blood-brain barrier breakdown, Microglia, Astrocyte, Receptors
Background Epilepsy is a neurological disorder, which is clinically defined as having at least two unprovoked seizures with an interval of more than 24 h; one unprovoked (or reflex) seizure whose recurrence risk exceeds 60% in the next ten years; or a confirmed epilepsy syndrome [1]. Almost 70 million people worldwide suffer from epilepsy [2], 30% of whom have failed to respond to medical management [3]. The causes of epilepsy can be divided into six categories: genetic, structural, metabolic, infectious, immune-associated, and unknown [4]. Although the precise and integrated mechanisms of epilepsy remain to be clarified, recent evidence has shown the involvement of changes in the neuronal ligand and voltage-gated ion channels, imbalance between excitatory and inhibitory neurotransmitters, oxidative stress, mitochondrial dysfunction, inflammatory and immune lesions, microglia and astrocyte activation, and blood-brain barrier (BBB) breakdown. Studies on epilepsy using both in vivo and in vitro experiments have verified the indispensable roles of inflammatory * Correspondence: [email protected] Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
mediators in epileptogenesis, including inflammatory molecules and cells, and BBB destruction. Proconvulsive events can initiate inflammatory processes through high mobility group protein 1 (HMGB1, also a damage-associated molecular pattern[DAMP]) and interleukin-1β (IL-1β), which are released from activated glial cells and stimulated neurons after pro-convulsive events and then bind to Toll-like receptors (
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