title: Causes of CNS inflammation and potential targets for anticonvulsants.
abstract: Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.
authors.affiliation: Department of Neurology, Epilepsy Unit, Hospital de Bellvitge, Feixa Llarga S/N, 08907 Hospitalet de Llobregat, Barcelona, Spain. mfalip@bellvitgehospital.cat
authors.forename: Mercé
authors.initials: M
authors.lastname: Falip
authors.forename: Xavier
authors.initials: X
authors.lastname: Salas-Puig
authors.forename: Carlos
authors.initials: C
authors.lastname: Cara
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D058990:Molecular Targeted Therapy; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D018836:Inflammation Mediators