{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:40:39Z","timestamp":1792651239321,"version":"4.5.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["602102"],"award-info":[{"award-number":["602102"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007109","name":"Universit\u00e0 degli Studi di Ferrara","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["neurotherapeuticsjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurotherapeutics"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1007\/s13311-022-01299-4","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T13:04:15Z","timestamp":1664543055000},"page":"1951-1965","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"title":["Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development"],"prefix":"10.1016","volume":"19","author":[{"given":"Annunziata","family":"Guarino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bettegazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimra","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Bochicchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Crippa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Sguizzato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Soukupova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9010-6447","authenticated-orcid":false,"given":"Silvia","family":"Zucchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Simonato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1007\/s13311-022-01299-4_bib1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/s41582-021-00461-4","article-title":"Identification of clinically relevant biomarkers of epileptogenesis - a strategic roadmap","volume":"17","author":"Simonato","year":"2021","journal-title":"Nat Rev Neurol"},{"issue":"11","key":"10.1007\/s13311-022-01299-4_bib2","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1111\/j.1528-1167.2012.03541.x","article-title":"Finding a better drug for epilepsy: preclinical screening strategies and experimental trial design","volume":"53","author":"Simonato","year":"2012","journal-title":"Epilepsia"},{"issue":"9","key":"10.1007\/s13311-022-01299-4_bib3","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S1474-4422(14)70076-6","article-title":"The challenge and promise of anti-epileptic therapy development in animal models","volume":"13","author":"Simonato","year":"2014","journal-title":"Lancet Neurol"},{"key":"10.1007\/s13311-022-01299-4_bib4","unstructured":"McNamara JO, Simonato M. Neurotrophic factors. In: Engel JJ, Moshe SL, editors. Epilepsy: a comprehensive textbook 3rd edition. Alphen aan den Rijn, Netherlands: Wolters Kluwer; in press."},{"issue":"1","key":"10.1007\/s13311-022-01299-4_bib5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1006\/exnr.1993.1186","article-title":"Seizure-induced changes in neurotrophin expression: implications for epilepsy","volume":"124","author":"Gall","year":"1993","journal-title":"Exp Neurol"},{"issue":"7","key":"10.1007\/s13311-022-01299-4_bib6","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1111\/j.1460-9568.1995.tb01148.x","article-title":"BDNF protein measured by a novel enzyme immunoassay in normal brain and after seizure: partial disagreement with mRNA levels","volume":"7","author":"Nawa","year":"1995","journal-title":"Eur J Neurosci"},{"issue":"3","key":"10.1007\/s13311-022-01299-4_bib7","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1046\/j.1460-9568.1998.00105.x","article-title":"Different patterns of induction of FGF-2, FGF-1 and BDNF mRNAs during kindling epileptogenesis in the rat","volume":"10","author":"Simonato","year":"1998","journal-title":"Eur J Neurosci"},{"issue":"11","key":"10.1007\/s13311-022-01299-4_bib8","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1523\/JNEUROSCI.19-11-04616.1999","article-title":"Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus","volume":"19","author":"Binder","year":"1999","journal-title":"J Neurosci"},{"issue":"17","key":"10.1007\/s13311-022-01299-4_bib9","doi-asserted-by":"crossref","first-page":"7502","DOI":"10.1523\/JNEUROSCI.22-17-07502.2002","article-title":"Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus","volume":"22","author":"He","year":"2002","journal-title":"J Neurosci"},{"issue":"17","key":"10.1007\/s13311-022-01299-4_bib10","doi-asserted-by":"crossref","first-page":"7191","DOI":"10.1073\/pnas.0810710106","article-title":"Localized delivery of fibroblast growth factor-2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model","volume":"106","author":"Paradiso","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1007\/s13311-022-01299-4_bib11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.nbd.2018.01.018","article-title":"Partial TrkB receptor activation suppresses cortical epileptogenesis through actions on parvalbumin interneurons","volume":"113","author":"Gu","year":"2018","journal-title":"Neurobiol Dis"},{"issue":"4","key":"10.1007\/s13311-022-01299-4_bib12","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/S0306-4522(99)00296-1","article-title":"Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex","volume":"93","author":"Croll","year":"1999","journal-title":"Neuroscience"},{"key":"10.1007\/s13311-022-01299-4_bib13","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuroscience.2014.12.036","article-title":"Expansion of the dentate mossy fiber-CA3 projection in the brain-derived neurotrophic factor-enriched mouse hippocampus","volume":"288","author":"Isgor","year":"2015","journal-title":"Neuroscience"},{"issue":"2","key":"10.1007\/s13311-022-01299-4_bib14","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1006\/exnr.1995.1024","article-title":"Suppressed epileptogenesis in BDNF mutant mice","volume":"133","author":"Kokaia","year":"1995","journal-title":"Exp Neurol"},{"issue":"4","key":"10.1007\/s13311-022-01299-4_bib15","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1523\/JNEUROSCI.19-04-01424.1999","article-title":"Selective inhibition of kindling development by intraventricular administration of TrkB receptor body","volume":"19","author":"Binder","year":"1999","journal-title":"J Neurosci"},{"issue":"1","key":"10.1007\/s13311-022-01299-4_bib16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.neuron.2013.04.027","article-title":"Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy","volume":"79","author":"Liu","year":"2013","journal-title":"Neuron"},{"issue":"3","key":"10.1007\/s13311-022-01299-4_bib17","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.neuron.2015.09.032","article-title":"A peptide uncoupling BDNF receptor TrkB from phospholipase Cgamma1 prevents epilepsy induced by status epilepticus","volume":"88","author":"Gu","year":"2015","journal-title":"Neuron"},{"key":"10.1007\/s13311-022-01299-4_bib18","first-page":"1","article-title":"Treatment with the flavonoid 7,8-dihydroxyflavone: a promising strategy for a constellation of body and brain disorders","author":"Emili","year":"2020","journal-title":"Crit Rev Food Sci Nutr"},{"issue":"2","key":"10.1007\/s13311-022-01299-4_bib19","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1248\/bpb.32.166","article-title":"Preventive effect of 7,8-dihydroxyflavone against oxidative stress induced genotoxicity","volume":"32","author":"Zhang","year":"2009","journal-title":"Biol Pharm Bull"},{"key":"10.1007\/s13311-022-01299-4_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2019.107742","article-title":"Inflammation and reactive oxygen species as disease modifiers in epilepsy","volume":"167","author":"Terrone","year":"2020","journal-title":"Neuropharmacology"},{"issue":"4","key":"10.1007\/s13311-022-01299-4_bib21","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/jcbfm.2010.220","article-title":"Animal research: reporting in vivo experiments--the ARRIVE guidelines.","volume":"31","author":"Kilkenny","year":"2011","journal-title":"J Cereb Blood Flow Metab."},{"key":"10.1007\/s13311-022-01299-4_bib22","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jneumeth.2015.09.007","article-title":"Opportunities for improving animal welfare in rodent models of epilepsy and seizures","volume":"260","author":"Lidster","year":"2016","journal-title":"J Neurosci Methods"},{"issue":"3","key":"10.1007\/s13311-022-01299-4_bib23","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation","volume":"32","author":"Racine","year":"1972","journal-title":"II Motor seizure Electroencephalogr Clin Neurophysiol"},{"key":"10.1007\/s13311-022-01299-4_bib24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.nbd.2014.12.015","article-title":"Effective termination of status epilepticus by rational polypharmacy in the lithium-pilocarpine model in rats: Window of opportunity to prevent epilepsy and prediction of epilepsy by biomarkers","volume":"75","author":"Brandt","year":"2015","journal-title":"Neurobiol Dis"},{"issue":"6","key":"10.1007\/s13311-022-01299-4_bib25","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1073\/pnas.0913572107","article-title":"A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone","volume":"107","author":"Jang","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"10.1007\/s13311-022-01299-4_bib26","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1176\/appi.ajp.2010.10030326","article-title":"Effect of 7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning","volume":"168","author":"Andero","year":"2011","journal-title":"Am J Psychiatry"},{"key":"10.1007\/s13311-022-01299-4_bib27","series-title":"The rat brain in stereotaxic coordinates","author":"Paxinos","year":"2013"},{"issue":"3","key":"10.1007\/s13311-022-01299-4_bib28","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1528-1167.2010.02930.x","article-title":"Localized overexpression of FGF-2 and BDNF in hippocampus reduces mossy fiber sprouting and spontaneous seizures up to 4 weeks after pilocarpine-induced status epilepticus","volume":"52","author":"Paradiso","year":"2011","journal-title":"Epilepsia"},{"issue":"Pt A","key":"10.1007\/s13311-022-01299-4_bib29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.brainresbull.2015.08.006","article-title":"The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders","volume":"119","author":"Tchekalarova","year":"2015","journal-title":"Brain Res Bull"},{"issue":"2","key":"10.1007\/s13311-022-01299-4_bib30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.bbr.2004.11.006","article-title":"Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks","volume":"159","author":"Ennaceur","year":"2005","journal-title":"Behav Brain Res"},{"issue":"7","key":"10.1007\/s13311-022-01299-4_bib31","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"10.1007\/s13311-022-01299-4_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2021.174068","article-title":"Anti-epileptogenic effect of NRP2945 in the pilocarpine model of temporal lobe epilepsy","volume":"901","author":"Lovisari","year":"2021","journal-title":"Eur J Pharmacol"},{"issue":"8","key":"10.1007\/s13311-022-01299-4_bib33","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/s41419-021-04062-3","article-title":"Casein kinase 2 dependent phosphorylation of eIF4B regulates BACE1 expression in Alzheimer's disease","volume":"12","author":"Bettegazzi","year":"2021","journal-title":"Cell Death Dis"},{"key":"10.1007\/s13311-022-01299-4_bib34","article-title":"Novel object recognition and object location behavioral testing in mice on a budget.","volume":"141","author":"Denninger","year":"2018","journal-title":"J Vis Exp."},{"key":"10.1007\/s13311-022-01299-4_bib35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/1742-2094-7-81","article-title":"Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures","volume":"7","author":"Bovolenta","year":"2010","journal-title":"J Neuroinflammation"},{"issue":"1473","key":"10.1007\/s13311-022-01299-4_bib36","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1098\/rstb.2006.1894","article-title":"Neurotrophin-regulated signalling pathways","volume":"361","author":"Reichardt","year":"2006","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"23","key":"10.1007\/s13311-022-01299-4_bib37","doi-asserted-by":"crossref","first-page":"4624","DOI":"10.1523\/JNEUROSCI.2939-18.2019","article-title":"TrkB-Shc signaling protects against hippocampal injury following status epilepticus","volume":"39","author":"Huang","year":"2019","journal-title":"J Neurosci"},{"key":"10.1007\/s13311-022-01299-4_bib38","doi-asserted-by":"crossref","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: an overview","volume":"5","author":"Panche","year":"2016","journal-title":"J Nutr Sci"},{"issue":"1","key":"10.1007\/s13311-022-01299-4_bib39","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/ana.24414","article-title":"Predicting and treating stress-induced vulnerability to epilepsy and depression","volume":"78","author":"Becker","year":"2015","journal-title":"Ann Neurol"},{"key":"10.1007\/s13311-022-01299-4_bib40","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.canlet.2019.03.022","article-title":"Dietary phytochemicals with anti-oxidant and pro-oxidant activities: a double-edged sword in relation to adjuvant chemotherapy and radiotherapy?","volume":"452","author":"Fernando","year":"2019","journal-title":"Cancer Lett"},{"issue":"40","key":"10.1007\/s13311-022-01299-4_bib41","doi-asserted-by":"crossref","first-page":"27571","DOI":"10.1074\/jbc.M114.562561","article-title":"Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor","volume":"289","author":"Liu","year":"2014","journal-title":"J Biol Chem"},{"key":"10.1007\/s13311-022-01299-4_bib42","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.yebeh.2015.09.028","article-title":"Novel combinations of phenotypic biomarkers predict development of epilepsy in the lithium-pilocarpine model of temporal lobe epilepsy in rats","volume":"53","author":"Broer","year":"2015","journal-title":"Epilepsy Behav"},{"key":"10.1007\/s13311-022-01299-4_bib43","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.nbd.2016.05.001","article-title":"Cognitive deficits and brain myo-Inositol are early biomarkers of epileptogenesis in a rat model of epilepsy","volume":"93","author":"Pascente","year":"2016","journal-title":"Neurobiol Dis"},{"issue":"9","key":"10.1007\/s13311-022-01299-4_bib44","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1111\/epi.16632","article-title":"Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid-percussion injury in rats","volume":"61","author":"Lapinlampi","year":"2020","journal-title":"Epilepsia"},{"issue":"1","key":"10.1007\/s13311-022-01299-4_bib45","doi-asserted-by":"crossref","first-page":"8665","DOI":"10.1038\/s41598-021-88088-9","article-title":"Behavioral characteristics as potential biomarkers of the development and phenotype of epilepsy in a rat model of temporal lobe epilepsy","volume":"11","author":"Nizinska","year":"2021","journal-title":"Sci Rep"}],"container-title":["Neurotherapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-022-01299-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13311-022-01299-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923001472?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923001472?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-022-01299-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:35:21Z","timestamp":1761806121000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1878747923001472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["S1878747923001472"],"URL":"https:\/\/doi.org\/10.1007\/s13311-022-01299-4","relation":{},"ISSN":["1878-7479"],"issn-type":[{"value":"1878-7479","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development","name":"articletitle","label":"Article Title"},{"value":"Neurotherapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1007\/s13311-022-01299-4","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2022 The Author(s). Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}