High Mobility Group Box 1 is a novel pathogenic factor and a mechanistic biomarker for epilepsy

Publication date: August 2018Source: Brain, Behavior, and Immunity, Volume 72Author(s): Teresa Ravizza, Gaetano Terrone, Alessia Salamone, Federica Frigerio, Silvia Balosso, Daniel J. Antoine, Annamaria VezzaniAbstractApproximately 30% of epilepsy patients experience seizures that are not controlled by the available drugs. Moreover, these drugs provide mainly a symptomatic treatment since they do not interfere with the disease’s mechanisms. A mechanistic approach to the discovery of key pathogenic brain modifications causing seizure onset, recurrence and progression is instrumental for designing novel and rationale therapeutic interventions that could modify the disease course or prevent its development. In this regard, increasing evidence shows that neuroinflammation is a pathogenic factor in drug-resistant epilepsies. The High Mobility Group Box 1 (HMGB1)/Toll-like receptor 4 axis is a key initiator of neuroinflammation following brain injuries leading to epilepsy, and its activation contributes to seizure mechanisms in animal models. Recent findings have shown dynamic changes in HMGB1 and its isoforms in the brain and blood of animals exposed to acute brain injuries and undergoing epileptogenesis, and in surgically resected epileptic foci in humans. HMGB1 isoforms reflect different pathophysiological processes, and the disulfide isoform, which is generated in the brain during oxidative stress, is implicated in seizures, cell loss and cognitive dysfunctions. Interfering w...

Source: Brain, Behavior, and Immunity - July 11, 2018 Category: Neurology Source Type: research