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Whether chronic activation of anti\u2010oxidant pathways is beneficial or contributes to pathology is not clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated oxidative stress markers, including haem oxygenase 1, ferritin and the inflammation associated microRNA\u2010155 in surgically resected epileptogenic brain tissue of TSC (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) and FCD IIb (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) patients and in a TSC model (<jats:italic>Tsc1<\/jats:italic><jats:sup>GFAP\u2212\/\u2212<\/jats:sup>mice) using immunohistochemistry,<jats:italic>in situ<\/jats:italic>hybridization, real\u2010time quantitative PCR and immunoblotting. Using human foetal astrocytes we performed an<jats:italic>in vitro<\/jats:italic>characterization of the anti\u2010oxidant response to acute and chronic oxidative stress and evaluated overexpression of the disease\u2010relevant pro\u2010inflammatory microRNA\u2010155.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Resected TSC or FCD IIb tissue displayed higher expression of oxidative stress markers and microRNA\u2010155.<jats:italic>Tsc1<\/jats:italic><jats:sup>GFAP\u2212\/\u2212<\/jats:sup>mice expressed more microRNA\u2010155 and haem oxygenase 1 in the brain compared to wild\u2010type, preceding the typical development of spontaneous seizures in these animals.<jats:italic>In vitro<\/jats:italic>, chronic microRNA\u2010155 overexpression induced haem oxygenase 1, iron regulatory elements and increased susceptibility to oxidative stress. Overexpression of iron regulatory genes was also detected in patients with TSC, FCD IIb and<jats:italic>Tsc1<\/jats:italic><jats:sup>GFAP\u2212\/\u2212<\/jats:sup>mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that early and sustained activation of anti\u2010oxidant signalling and dysregulation of iron metabolism are a pathological hallmark of FCD IIb and TSC. Our findings suggest novel therapeutic strategies aimed at controlling the pathological link between both processes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12596","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T18:22:31Z","timestamp":1577125351000},"page":"546-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Chronic activation of anti\u2010oxidant pathways and iron accumulation in epileptogenic malformations"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-3697","authenticated-orcid":false,"given":"T. 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