Glia as a source of cytokines: implications for neuronal excitability and survival.
In the last decade, preclinical studies have provided a better characterization of the homeostatic and maladaptive mechanisms occurring either during the process of epileptogenesis or after the permanent epileptic state has emerged. Experimental evidence supported by clinical observations highlighted the possibility that brain inflammation is a common factor contributing, or predisposing, to the occurrence of seizures and cell death, in various forms of epilepsy of different etiologies. Expression of proinflammatory cytokines, as a hallmark of brain inflammation, has been demonstrated in glia in various experimental models of seizures and in human epilepsies. Experimental studies in rodents with perturbed cytokine systems indicate that these inflammatory mediators can alter neuronal excitability and affect cell survival by activating transcriptional and posttranslational intracellular pathways. This paper will provide an overview on the current knowledge in this field to discuss mechanistic hypotheses into the study of pathogenesis of epilepsy and recognize new potential therapeutic options.
Vezzani
Annamaria
A
Mario Negri Institute for Pharmacological Research, Milano, Italy. vezzani@marionegri.it
Ravizza
Teresa
T
Balosso
Silvia
S
Aronica
Eleonora
E
D000818:Animals; D016923:Cell Death; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology*; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology; D008959:Models, Neurological; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D012377:Rodentia; D012598:Sclerosis
D016207:Cytokines; D007378:Interleukins