%0 Journal Article %J PLoS OnePLoS OnePLoS One %D 2018 %T Glial responses during epileptogenesis in Mus musculus point to potential therapeutic targets %A Kalozoumi, G. %A Kel-Margoulis, O. %A Vafiadaki, E. %A Greenberg, D. %A Bernard, H. %A Soreq, H. %A Depaulis, A. %A Sanoudou, D. %K Animals %K Anticonvulsants/*pharmacology %K Cell Death/drug effects %K Computational Biology %K computer simulation %K Disease Models, Animal %K Epilepsy, Temporal Lobe/*drug therapy/immunology %K Gene Expression Regulation/drug effects %K Hippocampus/drug effects/immunology %K Kainic Acid %K Male %K Mice, Inbred C57BL %K MicroRNAs/metabolism %K Neuroglia/*drug effects/immunology %K Status Epilepticus/*drug therapy/immunology %X The Mesio-Temporal Lobe Epilepsy syndrome is the most common form of intractable epilepsy. It is characterized by recurrence of focal seizures and is often associated with hippocampal sclerosis and drug resistance. We aimed to characterize the molecular changes occurring during the initial stages of epileptogenesis in search of new therapeutic targets for Mesio-Temporal Lobe Epilepsy. We used a mouse model obtained by intra-hippocampal microinjection of kainate and performed hippocampal whole genome expression analysis at 6h, 12h and 24h post-injection, followed by multilevel bioinformatics analysis. We report significant changes in immune and inflammatory responses, neuronal network reorganization processes and glial functions, predominantly initiated during status epilepticus at 12h and persistent after the end of status epilepticus at 24h post-kainate. Upstream regulator analysis highlighted Cyba, Cybb and Vim as central regulators of multiple overexpressed genes implicated in glial responses at 24h. In silico microRNA analysis indicated that miR-9, miR-19b, miR-129, and miR-223 may regulate the expression of glial-associated genes at 24h. Our data support the hypothesis that glial-mediated inflammatory response holds a key role during epileptogenesis, and that microglial cells may participate in the initial process of epileptogenesis through increased ROS production via the NOX complex. %B PLoS OnePLoS OnePLoS One %V 13 %P e0201742 %@ 1932-6203 (Electronic)1932-6203 (Linking) %G eng %M 30114263 %2 6095496 GmbH (http://genexplain.com/) at the time of the study. This commercial affiliation does not alter our adherence PLOS ONE policies on sharing data and materials. %! PloS onePloS one