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We investigated whether expression of OS and brain inflammation markers co\u2010occurred also in resected brain tissue of patients with epileptogenic cortical malformations: hemimegalencephaly (HME), focal cortical dysplasia (FCD) and cortical tubers in tuberous sclerosis complex (TSC). Moreover, we studied molecular mechanisms linking OS and inflammation in an <jats:italic>in vitro<\/jats:italic> model of neuronal function. Untangling interdependency and underlying molecular mechanisms might pose new therapeutic strategies for treating patients with drug\u2010resistant epilepsy of different etiologies. Immunohistochemistry was performed for specific OS markers xCT and iNOS and brain inflammation markers TLR4, COX\u20102 and NF\u2010\u03baB in cortical tissue derived from patients with HME, FCD IIa, IIb and TSC. Additionally, we studied gene expression of these markers using the human neuronal cell line SH\u2010SY5Y in which OS was induced using H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. OS markers were higher in dysmorphic neurons and balloon\/giant cells in cortex of patients with FCD IIb or TSC. Expression of OS markers was positively correlated to expression of brain inflammation markers. <jats:italic>In vitro<\/jats:italic>, 100\u00a0\u00b5M, but not 50\u00a0\u00b5M, of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> increased expression of <jats:italic>TLR4<\/jats:italic>, <jats:italic>IL\u20101\u03b2<\/jats:italic> and <jats:italic>COX\u20102<\/jats:italic>. We found that NF\u2010\u03baB signaling was activated only upon stimulation with 100\u00a0\u00b5M H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> leading to upregulation of TLR4 signaling and <jats:italic>IL\u20101\u03b2<\/jats:italic>. The NF\u2010\u03baB inhibitor TPCA\u20101 completely reversed this effect. Our results show that OS positively correlates with neuroinflammation and is particularly evident in brain tissue of patients with FCD IIb and TSC. <jats:italic>In vitro<\/jats:italic>, NF\u2010\u03baB is involved in the switch to an inflammatory state after OS. We propose that the extent of OS can predict the neuroinflammatory state of the brain. Additionally, antioxidant treatments may prevent the switch to inflammation in neurons thus targeting multiple epileptogenic processes at once.<\/jats:p>","DOI":"10.1111\/bpa.12661","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T19:03:43Z","timestamp":1539198223000},"page":"351-365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence"],"prefix":"10.1111","volume":"29","author":[{"given":"Andrea","family":"Arena","sequence":"first","affiliation":[{"name":"Department of (Neuro\u2010)Pathology, Amsterdam UMC University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9 Amsterdam the Netherlands"},{"name":"Department of Biochemical Sciences Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till 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