New evidences of inflammatory mediators in absence epilepsy

L'epilessia dell'assenza appartiene alle forme di epilessia di tipo generalizzato. Crisi di assenza sono caratterizzate a livello elettroencefalografico dall'insorgenza di onde-punta caratteristiche (SWDs) dovute ad una patologica attività sincronizzata del circuito talamo-corticale. Gli studi sono stati effettuati sul modello animale (Wag/Rij), ratti che dal sesto mese d'età presentano crisi di epilessia dell'assenza ricorrenti e spontanee. Ratti Wag/rij di quattro mesi d’età non ancora epilettici sono stati utilizzati come controllo. La più recente teoria volta a spiegare le cause dell'insorgenza di questa patologia mette in luce il ruolo primario della corteccia cerebrale ed identifica nella regione peri-orale della corteccia somato-sensoriale il focus di inizio delle crisi. Al fine di avvalorare tale teoria, sono stati svolti studi di risonanza magnetica strutturale (T2 e DWI) e funzionale (rCBV e rCBF), esperimenti di spettroscopia di risonanza magnetica (MRS) e analisi del profilo di espressione genica nelle aree cerebrali maggiormente coinvolte in questa patologia. Inoltre, la registrazione e l'analisi di tracciati EEG in seguito al trattamento con IL-1β e TNF-α hanno messo in luce il ruolo di tali citochine infiammatorie sull'insorgenza e la modulazione delle crisi d'assenza.Absence epilepsy is the most pure form of generalized epilepsy characterized in the EEG by widespread bilaterally synchronous spike-wave discharges (SWDs) caused by thalamo-cortical oscillations. Latest Cortical Focus theory suggests a consistent cortical “focus” within the peri-oral region of the somatosensory cortex. In order to raise the evidence of a focal cortical theory, structural and functional MRI data were collected in all the cerebral areas involved in spindles generation and propagation in a genetic model of absence epilepsy. Four-months-old WAG/Rij rats were used as control (no SWDs) whereas nine-months-old rats (daily SWDs) were referred as experimental group. In order to exacerbate SWDs episodes, rats were treated with Vigabatrin. Moreover to provides chemical information about different brain regions in Wag/Rij rats, we performed MRS analysis for the measure of the levels of different metabolites which reflects specific cellular and biochemical processes. It has become increasingly obvious during recent decades that genetic factors play a main role in the idiopathic generalized epilepsies, including absence epilepsy. In this view, gene-array analysis for cell signaling pathways involved in SWDs in different cerebral areas, and qPCR data were performed and correlated with EEG data. The actions of proinflammatory cytokines in the CNS are only partially discovered. Some cytokines have been recently shown to affect neurotransmitters or are required to preserve the synaptic strength at excitatory synapses, or affect the expression of various neuropeptides and neurotrophic factors in several brain regions. Changes in the immune system may change the excitability of the CNS and alter the susceptibility of exogenous induced or genetically determined types of epilepsy. Here we investigate the role of two cytokines, IL-1β and TNF-α in WAG/Rij rats. Our hypothesis is that cerebral blood flow alterations and cytokines/chemokines release can modulate the occurrence of SWDs. Both controls and WAG/Rij rats were injected i.p. by TNF-α (2µg/kg) and IL-1β (2µg/kg) and EEG was recordered for 72h after the treatment. Furthermore, we analyzed the blood serum by ELISA method for TNF-α and IL-1β in control and epileptic animals