Neuroinflammatory targets and treatments for epilepsy validated in experimental models
Authors listEleonora Aronica Sebastian Bauer Yuri Bozzi Matteo Caleo Raymond Dingledine Jan A Gorter David C Henshall Daniela Kaufer Sookyong Koh Wolfgang Löscher Jean-Pierre Louboutin Michele Mishto Braxton A Norwood Eleonora Palma Michael O Poulter Gaetano Terrone Annamaria Vezzani Rafal M Kaminski
A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries.