{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:44:27Z","timestamp":1792021467265,"version":"4.4.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"European Union\u2019s Seventh Framework Programme","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1 NS086423"],"award-info":[{"award-number":["RO1 NS086423"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1NS039587"],"award-info":[{"award-number":["RO1NS039587"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease\u2014preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs, we focused on oxidative stress since it is a pathophysiological process commonly occurring in experimental epileptogenesis and observed in human epilepsy. Using a rat model of acquired epilepsy induced by electrical status epilepticus, we show that oxidative stress occurs in both neurons and astrocytes during epileptogenesis, as assessed by measuring biochemical and histological markers. This evidence was validated in the hippocampus of humans who died following status epilepticus. Oxidative stress was reduced in animals undergoing epileptogenesis by a transient treatment with N-acetylcysteine and sulforaphane, which act to increase glutathione levels through complementary mechanisms. These antioxidant drugs are already used in humans for other therapeutic indications. This drug combination transiently administered for 2 weeks during epileptogenesis inhibited oxidative stress more efficiently than either drug alone. The drug combination significantly delayed the onset of epilepsy, blocked disease progression between 2 and 5 months post-status epilepticus and drastically reduced the frequency of spontaneous seizures measured at 5 months without modifying the average seizure duration or the incidence of epilepsy in animals. Treatment also decreased hippocampal neuron loss and rescued cognitive deficits. Oxidative stress during epileptogenesis was associated with de novo brain and blood generation of high mobility group box 1 (HMGB1), a neuroinflammatory molecule implicated in seizure mechanisms. Drug-induced reduction of oxidative stress prevented HMGB1 generation, thus highlighting a potential novel mechanism contributing to therapeutic effects. Our data show that targeting oxidative stress with clinically used drugs for a limited time window starting early after injury significantly improves long-term disease outcomes. This intervention may be considered for patients exposed to potential epileptogenic insults.<\/jats:p>","DOI":"10.1093\/brain\/awz130","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T15:16:22Z","timestamp":1556118982000},"page":"e39-e39","source":"Crossref","is-referenced-by-count":200,"title":["Targeting oxidative stress improves disease outcomes in a rat model of acquired epilepsy"],"prefix":"10.1093","volume":"142","author":[{"given":"Alberto","family":"Pauletti","sequence":"first","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Terrone","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawfeeq","family":"Shekh-Ahmad","sequence":"additional","affiliation":[{"name":"2 Department of Clinical and Experimental Epilepsy, University College London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Salamone","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ravizza","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Rizzi","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pastore","sequence":"additional","affiliation":[{"name":"3 Metabolomics and Proteomics Unit, \u2018Bambino Ges\u00f9\u2019 Children\u2019s Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Pascente","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ping","family":"Liang","sequence":"additional","affiliation":[{"name":"4 Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca R","family":"Villa","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Balosso","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey Y","family":"Abramov","sequence":"additional","affiliation":[{"name":"2 Department of Clinical and Experimental Epilepsy, University College London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin A","family":"van Vliet","sequence":"additional","affiliation":[{"name":"5 Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"Del Giudice","sequence":"additional","affiliation":[{"name":"6 Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[{"name":"5 Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands"},{"name":"7 Stichting Epilepsie Instellingen Nederland, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Patel","sequence":"additional","affiliation":[{"name":"4 Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Walker","sequence":"additional","affiliation":[{"name":"2 Department of Clinical and Experimental Epilepsy, University College London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Vezzani","sequence":"additional","affiliation":[{"name":"1 Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,30]]},"reference":[{"key":"2019070505430552400_awz130-B1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.freeradbiomed.2011.03.039","article-title":"Nitric oxide activates an Nrf2\/sulfiredoxin antioxidant pathway in macrophages","volume":"51","author":"Abbas","year":"2011","journal-title":"Free Radic Biol Med"},{"key":"2019070505430552400_awz130-B4","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/14734220601142878","article-title":"N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology","volume":"6","author":"Arakawa","year":"2007","journal-title":"Cerebellum"},{"key":"2019070505430552400_awz130-B5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1528-1167.2011.03033.x","article-title":"Inflammation in epilepsy: clinical observations","volume":"52","author":"Aronica","year":"2011","journal-title":"Epilepsia"},{"key":"2019070505430552400_awz130-B6","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1089\/ars.2013.5349","article-title":"Disulfide-containing high mobility group box-1 promotes N-methyl-d-aspartate receptor function and excitotoxicity by activating Toll-like receptor 4-dependent signaling in hippocampal neurons","volume":"21","author":"Balosso","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"2019070505430552400_awz130-B7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.neulet.2007.01.057","article-title":"Effects of the vitamin E in catalase activities in hippocampus after status epilepticus induced by pilocarpine in Wistar rats","volume":"416","author":"Barros","year":"2007","journal-title":"Neurosci Lett"},{"key":"2019070505430552400_awz130-B8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0920-1211(00)00096-6","article-title":"Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies","volume":"40","author":"Ben-Menachem","year":"2000","journal-title":"Epilepsy Res"},{"key":"2019070505430552400_awz130-B9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.expneurol.2015.06.012","article-title":"Oxidative stress in murine Theiler\u2019s virus-induced temporal lobe epilepsy","volume":"271","author":"Bhuyan","year":"2015","journal-title":"Exp Neurol"},{"key":"2019070505430552400_awz130-B10","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/epi.12220","article-title":"International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a task force report from the ILAE commission on diagnostic methods","volume":"54","author":"Blumcke","year":"2013","journal-title":"Epilepsia"},{"key":"2019070505430552400_awz130-B11","doi-asserted-by":"crossref","first-page":"759293","DOI":"10.1155\/2014\/759293","article-title":"Relevance of the glutathione system in temporal lobe epilepsy: evidence in human and experimental models","volume":"2014","author":"Cardenas-Rodriguez","year":"2014","journal-title":"Oxid Med Cell Longev"},{"key":"2019070505430552400_awz130-B12","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1158\/1940-6207.CAPR-14-0459","article-title":"Effect of Sulforaphane in men with biochemical recurrence after radical prostatectomy","volume":"8","author":"Cipolla","year":"2015","journal-title":"Cancer Prev Res"},{"key":"2019070505430552400_awz130-B13","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1046\/j.1460-9568.2000.00140.x","article-title":"Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus","volume":"12","author":"De Simoni","year":"2000","journal-title":"Eur J Neurosci"},{"key":"2019070505430552400_awz130-B14","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.neubiorev.2015.04.015","article-title":"Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review","volume":"55","author":"Deepmala","year":"2015","journal-title":"Neurosci Biobehav Rev"},{"key":"2019070505430552400_awz130-B15","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1007\/s12035-015-9451-4","article-title":"Sulforaphane ameliorates okadaic acid-induced memory impairment in rats by activating the Nrf2\/HO\u20101 antioxidant pathway","volume":"53","author":"Dwivedi","year":"2015","journal-title":"Mol Neurobiol"},{"key":"2019070505430552400_awz130-B16","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1046\/j.1471-4159.2003.01580.x","article-title":"The antioxidant alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice","volume":"84","author":"Farr","year":"2003","journal-title":"J Neurochem"},{"key":"2019070505430552400_awz130-B17","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1111\/j.1528-1167.2012.03685.x","article-title":"In vivo imaging of glia activation using 1 H-magnetic resonance spectroscopy to detect putative biomarkers of tissue epileptogenicity","volume":"53","author":"Filibian","year":"2012","journal-title":"Epilepsia"},{"key":"2019070505430552400_awz130-B18","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1046\/j.1460-9568.2001.01428.x","article-title":"Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons","volume":"13","author":"Gorter","year":"2001","journal-title":"Eur J Neurosci"},{"key":"2019070505430552400_awz130-B19","doi-asserted-by":"crossref","first-page":"10082","DOI":"10.1523\/JNEUROSCI.19-22-10082.1999","article-title":"Total number and ratio of excitatory and inhibitory synapses converging onto single interneurons of different types in the CA1 area of the rat hippocampus","volume":"19","author":"Gulyas","year":"1999","journal-title":"J Neurosci"},{"key":"2019070505430552400_awz130-B20","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s11064-007-9466-y","article-title":"Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum","volume":"33","author":"Harvey","year":"2008","journal-title":"Neurochem Res"},{"key":"2019070505430552400_awz130-B21","volume-title":"The neuron in tissue culture","author":"Haynes","year":"1999"},{"key":"2019070505430552400_awz130-B22","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.coph.2007.07.005","article-title":"Modulators of neuronal cell death in epilepsy","volume":"8","author":"Henshall","year":"2008","journal-title":"Curr Opin Pharmacol"},{"key":"2019070505430552400_awz130-B23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2165\/00003088-199120020-00004","article-title":"Clinical pharmacokinetics of N-acetylcysteine","volume":"20","author":"Holdiness","year":"1991","journal-title":"Clin Pharmacokinet"},{"key":"2019070505430552400_awz130-B24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/WNF.0b013e31829ae713","article-title":"N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases","volume":"36","author":"Holmay","year":"2013","journal-title":"Clin Neuropharmacol"},{"key":"2019070505430552400_awz130-B25","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/aps.2010.101","article-title":"The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice","volume":"31","author":"Hong","year":"2010","journal-title":"Acta Pharmacol Sin"},{"key":"2019070505430552400_awz130-B26","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/nure.12060","article-title":"Sulforaphane: translational research from laboratory bench to clinic","volume":"71","author":"Houghton","year":"2013","journal-title":"Nutr Rev"},{"key":"2019070505430552400_awz130-B27","doi-asserted-by":"crossref","first-page":"484613","DOI":"10.1155\/2013\/484613","article-title":"Role of redox signaling in neuroinflammation and neurodegenerative diseases","volume":"2013","author":"Hsieh","year":"2013","journal-title":"Biomed Res Int"},{"key":"2019070505430552400_awz130-B28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1124\/jpet.103.064261","article-title":"In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat","volume":"310","author":"Hu","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"key":"2019070505430552400_awz130-B29","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.nbd.2013.03.006","article-title":"Receptor for advanced glycation endproducts is upregulated in temporal lobe epilepsy and contributes to experimental seizures","volume":"58","author":"Iori","year":"2013","journal-title":"Neurobiol Dis"},{"key":"2019070505430552400_awz130-B30","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1093\/brain\/awh568","article-title":"Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans","volume":"128","author":"Kann","year":"2005","journal-title":"Brain"},{"key":"2019070505430552400_awz130-B31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1161\/01.STR.26.2.305","article-title":"N-acetylcysteine enhances hippocampal neuronal survival after transient forebrain ischemia in rats","volume":"26","author":"Knuckey","year":"1995","journal-title":"Stroke"},{"key":"2019070505430552400_awz130-B32","doi-asserted-by":"crossref","first-page":"e1442","DOI":"10.1038\/cddis.2014.390","article-title":"Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation","volume":"5","author":"Kovac","year":"2014","journal-title":"Cell Death Dis"},{"key":"2019070505430552400_awz130-B33","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","article-title":"Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies","volume":"51","author":"Kwan","year":"2010","journal-title":"Epilepsia"},{"key":"2019070505430552400_awz130-B34","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/0028-3908(93)90020-4","article-title":"Nitric oxide, superoxide and peroxynitrite: putative mediators of NMDA-induced cell death in cerebellar granule cells","volume":"32","author":"Lafon-Cazal","year":"1993","journal-title":"Neuropharmacology"},{"key":"2019070505430552400_awz130-B35","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0306-4522(00)00397-3","article-title":"Mitochondrial superoxide production in kainate-induced hippocampal damage","volume":"101","author":"Liang","year":"2000","journal-title":"Neuroscience"},{"key":"2019070505430552400_awz130-B36","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.freeradbiomed.2005.08.026","article-title":"Seizure-induced changes in mitochondrial redox status","volume":"40","author":"Liang","year":"2006","journal-title":"Free Radic Biol Med"},{"key":"2019070505430552400_awz130-B37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.redox.2016.05.004","article-title":"Plasma cysteine\/cystine redox couple disruption in animal models of temporal lobe epilepsy","volume":"9","author":"Liang","year":"2016","journal-title":"Redox Biol"},{"key":"2019070505430552400_awz130-B38","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1073\/pnas.1316925111","article-title":"JAK\/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation","volume":"111","author":"Lu","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019070505430552400_awz130-B39","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s13238-012-2118-2","article-title":"Regulation of HMGB1 release by inflammasomes","volume":"4","author":"Lu","year":"2013","journal-title":"Protein Cell"},{"key":"2019070505430552400_awz130-B41","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nm.2127","article-title":"Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures","volume":"16","author":"Maroso","year":"2010","journal-title":"Nat Med"},{"key":"2019070505430552400_awz130-B42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.expneurol.2011.08.012","article-title":"High-mobility group box-1 impairs memory in mice through both toll-like receptor 4 and receptor for advanced glycation end products","volume":"232","author":"Mazarati","year":"2011","journal-title":"Exp Neurol"},{"key":"2019070505430552400_awz130-B43","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ana.23940","article-title":"Nrf2 defense pathway: experimental evidence for its protective role in epilepsy","volume":"74","author":"Mazzuferi","year":"2013","journal-title":"Ann Neurol"},{"key":"2019070505430552400_awz130-B44","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.nbd.2013.07.015","article-title":"Pharmacological blockade of IL-1beta\/IL-1 receptor type 1 axis during epileptogenesis provides neuroprotection in two rat models of temporal lobe epilepsy","volume":"59","author":"No\u00e9","year":"2013","journal-title":"Neurobiol Dis"},{"key":"2019070505430552400_awz130-B45","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/brain\/awn079","article-title":"Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy","volume":"131","author":"No\u00e9","year":"2008","journal-title":"Brain"},{"key":"2019070505430552400_awz130-B47","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/clinchem\/44.4.825","article-title":"Fully automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine, and 2-mercaptopropionylglycine in plasma and urine","volume":"44","author":"Pastore","year":"1998","journal-title":"Clin Chem"},{"key":"2019070505430552400_awz130-B48","volume-title":"The rat brain in stereotaxic coordinates","author":"Paxinos","year":"2005"},{"key":"2019070505430552400_awz130-B49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.nbd.2015.07.005","article-title":"Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy","volume":"82","author":"Pearson","year":"2015","journal-title":"Neurobiol Dis"},{"key":"2019070505430552400_awz130-B50","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s13311-014-0257-2","article-title":"Past and present definitions of epileptogenesis and its biomarkers","volume":"11","author":"Pitkanen","year":"2014","journal-title":"Neurotherapeutics"},{"key":"2019070505430552400_awz130-B51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.eplepsyres.2004.10.003","article-title":"Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat","volume":"63","author":"Pitkanen","year":"2005","journal-title":"Epilepsy Res"},{"key":"2019070505430552400_awz130-B52","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1474-4422(02)00073-X","article-title":"Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy","volume":"1","author":"Pitkanen","year":"2002","journal-title":"Lancet Neurol"},{"key":"2019070505430552400_awz130-B53","doi-asserted-by":"crossref","first-page":"745613","DOI":"10.1155\/2015\/745613","article-title":"Seizure-induced oxidative stress in temporal lobe epilepsy","volume":"2015","author":"Puttachary","year":"2015","journal-title":"Biomed Res Int"},{"key":"2019070505430552400_awz130-B54","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.nbd.2016.05.013","article-title":"1400 W, a highly selective inducible nitric oxide synthase inhibitor is a potential disease modifier in the rat kainate model of temporal lobe epilepsy","volume":"93","author":"Puttachary","year":"2016","journal-title":"Neurobiol Dis"},{"key":"2019070505430552400_awz130-B55","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.nbd.2007.08.012","article-title":"Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy","volume":"29","author":"Ravizza","year":"2008","journal-title":"Neurobiol Dis"},{"key":"2019070505430552400_awz130-B56","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Reagan-Shaw","year":"2008","journal-title":"FASEB J"},{"key":"2019070505430552400_awz130-B57","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1523\/JNEUROSCI.15-05-03318.1995","article-title":"Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation","volume":"15","author":"Reynolds","year":"1995","journal-title":"J Neurosci"},{"key":"2019070505430552400_awz130-B58","doi-asserted-by":"crossref","first-page":"9897","DOI":"10.1073\/pnas.96.17.9897","article-title":"EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology","volume":"96","author":"Rong","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019070505430552400_awz130-B59","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.freeradbiomed.2013.02.002","article-title":"Mitochondrial involvement and oxidative stress in temporal lobe epilepsy","volume":"62","author":"Rowley","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"2019070505430552400_awz130-B60","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.nbd.2013.12.006","article-title":"Temporal and spatial increase of reactive nitrogen species in the kainate model of temporal lobe epilepsy","volume":"64","author":"Ryan","year":"2014","journal-title":"Neurobiol Dis"},{"key":"2019070505430552400_awz130-B61","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/epi.12052","article-title":"Does surgery prevent worsening of epilepsy?","volume":"54","author":"Schmidt","year":"2005","journal-title":"Epilepsia"},{"key":"2019070505430552400_awz130-B63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jns.2011.06.030","article-title":"The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury","volume":"308","author":"Silva","year":"2011","journal-title":"J Neurol Sci"},{"key":"2019070505430552400_awz130-B64","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.spen.2015.03.006","article-title":"Sleep in autism spectrum disorder and attention deficit hyperactivity disorder","volume":"22","author":"Singh","year":"2015","journal-title":"Semin Pediatr Neurol"},{"key":"2019070505430552400_awz130-B66","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.redox.2013.08.006","article-title":"Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells","volume":"1","author":"Steele","year":"2013","journal-title":"Redox Biol"},{"key":"2019070505430552400_awz130-B67","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4161\/cbt.9.2.10583","article-title":"N-acetylcysteine, reactive oxygen species and beyond","volume":"9","author":"Sun","year":"2010","journal-title":"Cancer Biol Ther"},{"key":"2019070505430552400_awz130-B68","first-page":"100","article-title":"The vulnerability of calretinin-containing hippocampal interneurons to temporal lobe epilepsy","volume":"8","author":"Toth","year":"2014","journal-title":"Front Neuroanat"},{"key":"2019070505430552400_awz130-B69","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-pharmtox-010814-124607","article-title":"Candidate drug targets for prevention or modification of epilepsy","volume":"55","author":"Varvel","year":"2015","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"2019070505430552400_awz130-B70","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1084\/jem.20120189","article-title":"Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release","volume":"209","author":"Venereau","year":"2012","journal-title":"J Exp Med"},{"key":"2019070505430552400_awz130-B71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.expneurol.2011.09.033","article-title":"Epilepsy and brain inflammation","volume":"244","author":"Vezzani","year":"2013","journal-title":"Exp Neurol"},{"key":"2019070505430552400_awz130-B72","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1586\/14737175.2015.1079130","article-title":"Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application","volume":"15","author":"Vezzani","year":"2015","journal-title":"Expert Rev Neurother"},{"key":"2019070505430552400_awz130-B73","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrneurol.2010.178","article-title":"The role of inflammation in epilepsy","volume":"7","author":"Vezzani","year":"2011","journal-title":"Nat Rev Neurol"},{"key":"2019070505430552400_awz130-B74","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.bbi.2011.03.018","article-title":"IL-1 receptor\/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures","volume":"25","author":"Vezzani","year":"2011","journal-title":"Brain Behav Immun"},{"key":"2019070505430552400_awz130-B75","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1111\/j.1471-4159.2010.07013.x","article-title":"Persistent impairment of mitochondrial and tissue redox status during lithium-pilocarpine-induced epileptogenesis","volume":"115","author":"Waldbaum","year":"2010","journal-title":"J Neurochem"},{"key":"2019070505430552400_awz130-B76","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1093\/chrsci\/49.10.801","article-title":"Development and validation of an LC-MS-MS method for the simultaneous determination of sulforaphane and its metabolites in rat plasma and its apllication in pharmacokinetics studies","volume":"49","author":"Wang","year":"2011","journal-title":"J Chromatogr Sci"},{"key":"2019070505430552400_awz130-B77","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.brainres.2013.12.004","article-title":"Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure","volume":"1544","author":"Wang","year":"2014","journal-title":"Brain Res"},{"key":"2019070505430552400_awz130-B78","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2119\/molmed.2011.00389","article-title":"Redox modification of cysteine residues regulates the cytokine activity of high mobility group box-1 (HMGB1)","volume":"18","author":"Yang","year":"2012","journal-title":"Mol Med"},{"key":"2019070505430552400_awz130-B79","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3389\/fphys.2015.00093","article-title":"Oxidative stress-mediated HMGB1 biology","volume":"6","author":"Yu","year":"2015","journal-title":"Front Physiol"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awz130\/28745314\/awz130.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/142\/7\/e39\/28906010\/awz130.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T12:55:45Z","timestamp":1607345745000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/142\/7\/e39\/5506575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,30]]},"references-count":73,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,5,30]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awz130","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.735855214.793566185","asserted-by":"object"}]},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,5,30]]}}}