title: Modulation of neuronal excitability by immune mediators in epilepsy.
abstract: A complex set of inflammatory molecules and their receptors has been described in epileptogenic foci in different forms of pharmacoresistant epilepsies. By activating receptor-mediated pathways in neurons, these molecules have profound neuromodulatory effects that are distinct from their canonical activation of immune functions. Importantly, the neuromodulatory actions of some inflammatory molecules contribute to hyperexcitability in neural networks that underlie seizures. This review summarizes recent findings related to the role of cytokines (IL-1beta and TNF-alpha) and danger signals (HMGB1) in decreasing seizure threshold, thereby contributing to seizure generation and the associated neuropathology. We will discuss preclinical studies suggesting that pharmacological inhibition of specific inflammatory signals may be useful to treat drug-resistant seizures in human epilepsy, and possibly arrest epileptogenesis in individuals at risk of developing the disease.
authors.affiliation: IRCCS-Mario Negri Institute for Pharmacological Research, Department of Neuroscience, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iori
authors.affiliation: IRCCS-Mario Negri Institute for Pharmacological Research, Department of Neuroscience, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Frigerio
authors.affiliation: IRCCS-Mario Negri Institute for Pharmacological Research, Department of Neuroscience, Milano, Italy. Electronic address: annamaria.vezzani@marionegri.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004827:Epilepsy / Q000276:immunology*; D006801:Humans; D009474:Neurons / Q000276:immunology*; D053573:Receptors, Interleukin-1 Type I / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D016207:Cytokines; C508590:IL1R1 protein, human; D053573:Receptors, Interleukin-1 Type I; D018124:Receptors, Tumor Necrosis Factor; D051193:Toll-Like Receptors