{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:00:38Z","timestamp":1788328838477,"version":"build-2803163510"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","epilepsybehavior.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Epilepsy &amp; Behavior"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.yebeh.2021.108509","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T11:34:47Z","timestamp":1643456087000},"page":"108509","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"special_numbering":"C","title":["Klotho alleviates NLRP3 inflammasome-mediated neuroinflammation in a temporal lobe epilepsy rat model by activating the Nrf2 signaling pathway"],"prefix":"10.1016","volume":"128","author":[{"given":"Tao","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yebeh.2021.108509_b0005","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1046\/j.1528-1157.2002.24101.x","article-title":"Memory outcome after selective amygdalohippocampectomy: a study in 140 patients with temporal lobe epilepsy","volume":"43","author":"Gleissner","year":"2002","journal-title":"Epilepsia"},{"key":"10.1016\/j.yebeh.2021.108509_b0010","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bandl.2017.08.007","article-title":"Epilepsy, language, and social skills","volume":"193","author":"Caplan","year":"2019","journal-title":"Brain Lang"},{"key":"10.1016\/j.yebeh.2021.108509_b0015","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.yebeh.2018.10.034","article-title":"Cognitive impairment and drug responsiveness in mesial temporal lobe epilepsy","volume":"90","author":"Celiker Uslu","year":"2019","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.yebeh.2021.108509_b0020","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.eplepsyres.2017.10.009","article-title":"Neuropsychological functioning and brain energetics of drug resistant mesial temporal lobe epilepsy patients","volume":"138","author":"Os\u00f3rio","year":"2017","journal-title":"Epilepsy Res"},{"key":"10.1016\/j.yebeh.2021.108509_b0025","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1001\/jamaneurol.2015.0941","article-title":"Neuroinflammation in temporal lobe epilepsy measured using positron emission tomographic imaging of translocator protein","volume":"72","author":"Gershen","year":"2015","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.yebeh.2021.108509_b0030","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejphar.2018.08.020","article-title":"Role of inflammation in epilepsy and neurobehavioral comorbidities: implication for therapy","volume":"837","author":"Paudel","year":"2018","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.yebeh.2021.108509_b0035","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.seizure.2021.07.028","article-title":"Temporal lobe epilepsy: evaluation of central and systemic immune-inflammatory features associated with drug resistance","volume":"91","author":"Toledo","year":"2021","journal-title":"Seizure"},{"key":"10.1016\/j.yebeh.2021.108509_b0040","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/imr.12286","article-title":"Initiation and perpetuation of NLRP3 inflammasome activation and assembly","volume":"265","author":"Elliott","year":"2015","journal-title":"Immunol Rev"},{"key":"10.1016\/j.yebeh.2021.108509_b0045","doi-asserted-by":"crossref","first-page":"106824","DOI":"10.1016\/j.intimp.2020.106824","article-title":"Transient receptor potential melastatin 2 contributes to neuroinflammation and negatively regulates cognitive outcomes in a pilocarpine-induced mouse model of epilepsy","volume":"87","author":"Hu","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.yebeh.2021.108509_b0050","doi-asserted-by":"crossref","first-page":"186","DOI":"10.2174\/1567202615666180731100224","article-title":"Curcumin reduces neuronal loss and inhibits the NLRP3 inflammasome activation in an epileptic rat model","volume":"15","author":"He","year":"2018","journal-title":"Curr Neurovasc Res"},{"key":"10.1016\/j.yebeh.2021.108509_b0055","doi-asserted-by":"crossref","DOI":"10.3390\/molecules25225474","article-title":"An overview of Nrf2 signaling pathway and its role in inflammation","volume":"25","author":"Saha","year":"2020","journal-title":"Molecules"},{"key":"10.1016\/j.yebeh.2021.108509_b0060","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1021\/tx700076q","article-title":"NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells","volume":"20","author":"Li","year":"2007","journal-title":"Chem Res Toxicol"},{"key":"10.1016\/j.yebeh.2021.108509_b0065","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"Kuro-o","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.yebeh.2021.108509_b0070","doi-asserted-by":"crossref","first-page":"147668","DOI":"10.1016\/j.brainres.2021.147668","article-title":"Klotho ameliorated cognitive deficits in a temporal lobe epilepsy rat model by inhibiting ferroptosis","volume":"1772","author":"Xiang","year":"2021","journal-title":"Brain Res"},{"key":"10.1016\/j.yebeh.2021.108509_b0075","doi-asserted-by":"crossref","first-page":"E11388","DOI":"10.1073\/pnas.1808609115","article-title":"Klotho controls the brain-immune system interface in the choroid plexus","volume":"115","author":"Zhu","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.yebeh.2021.108509_b0080","doi-asserted-by":"crossref","DOI":"10.3390\/cells9051231","article-title":"Focus on the role of Klotho protein in neuro-immune interactions in HT-22 cells upon LPS stimulation","volume":"9","author":"Rusinek","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.yebeh.2021.108509_b0085","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/HYPERTENSIONAHA.109.134320","article-title":"Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage","volume":"54","author":"Wang","year":"2009","journal-title":"Hypertension"},{"key":"10.1016\/j.yebeh.2021.108509_b0090","doi-asserted-by":"crossref","first-page":"5956","DOI":"10.7150\/thno.33872","article-title":"Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice","volume":"9","author":"Xian","year":"2019","journal-title":"Theranostics"},{"key":"10.1016\/j.yebeh.2021.108509_b0095","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jneumeth.2008.04.019","article-title":"The pilocarpine model of temporal lobe epilepsy","volume":"172","author":"Curia","year":"2008","journal-title":"J Neurosci Methods"},{"key":"10.1016\/j.yebeh.2021.108509_b0100","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation. II. Motor seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"10.1016\/j.yebeh.2021.108509_b0105","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1523\/JNEUROSCI.4056-03.2004","article-title":"Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus","volume":"24","author":"Richichi","year":"2004","journal-title":"J Neurosci"},{"key":"10.1016\/j.yebeh.2021.108509_b0110","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.bbr.2015.11.023","article-title":"Fractal dimensions: a new paradigm to assess spatial memory and learning using Morris water maze","volume":"299","author":"Singh","year":"2016","journal-title":"Behav Brain Res"},{"key":"10.1016\/j.yebeh.2021.108509_b0115","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.0013-9580.2004.37403.x","article-title":"Seizure, neuron loss, and mossy fiber sprouting in herpes simplex virus type 1-infected organotypic hippocampal cultures","volume":"45","author":"Chen","year":"2004","journal-title":"Epilepsia"},{"key":"10.1016\/j.yebeh.2021.108509_b0120","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1210\/er.2013-1079","article-title":"Molecular basis of Klotho: from gene to function in aging","volume":"36","author":"Xu","year":"2015","journal-title":"Endocr Rev"},{"key":"10.1016\/j.yebeh.2021.108509_b0125","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S1568-1637(02)00027-2","article-title":"Klotho: a fundamental regulator of aging","volume":"1","author":"Nabeshima","year":"2002","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.yebeh.2021.108509_b0130","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1134\/S0006297917090024","article-title":"Klotho protein: its role in aging and central nervous system pathology","volume":"82","author":"Boksha","year":"2017","journal-title":"Biochemistry (Mosc)"},{"key":"10.1016\/j.yebeh.2021.108509_b0135","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s12031-019-01356-2","article-title":"Klotho is neuroprotective in the superoxide dismutase (SOD1(G93A)) mouse model of ALS","volume":"69","author":"Zeldich","year":"2019","journal-title":"J Mol Neurosci"},{"key":"10.1016\/j.yebeh.2021.108509_b0140","doi-asserted-by":"crossref","first-page":"950","DOI":"10.3389\/fphar.2017.00950","article-title":"Protective effect of klotho against ischemic brain injury is associated with inhibition of RIG-I\/NF-kappaB signaling","volume":"8","author":"Zhou","year":"2017","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.yebeh.2021.108509_b0145","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1038\/mp.2017.211","article-title":"Secreted alphaKlotho isoform protects against age-dependent memory deficits","volume":"23","author":"Masso","year":"2018","journal-title":"Mol Psychiatry"},{"key":"10.1016\/j.yebeh.2021.108509_b0150","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2018.00734","article-title":"Protective role of L-3-n-butylphthalide in cognitive function and dysthymic disorders in mouse with chronic epilepsy","volume":"9","author":"Ye","year":"2018","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.yebeh.2021.108509_b0155","doi-asserted-by":"crossref","DOI":"10.1186\/1742-2094-10-53","article-title":"Hippocampal gene expression dysregulation of Klotho, nuclear factor kappa B and tumor necrosis factor in temporal lobe epilepsy patients","volume":"10","author":"Teocchi","year":"2013","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.yebeh.2021.108509_b0160","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/jnen\/nlw008","article-title":"Neuronal injury, gliosis, and glial proliferation in two models of temporal lobe epilepsy","volume":"75","author":"Loewen","year":"2016","journal-title":"J Neuropathol Exp Neurol"},{"key":"10.1016\/j.yebeh.2021.108509_b0165","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1007\/s004010050658","article-title":"Neuronal loss and gliosis of the amygdaloid nucleus in temporal lobe epilepsy. A quantitative analysis of 70 surgical specimens","volume":"93","author":"Wolf","year":"1997","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.yebeh.2021.108509_b0170","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12974-018-1247-9","article-title":"Effects of rapamycin and curcumin on inflammation and oxidative stress in vitro and in vivo - in search of potential anti-epileptogenic strategies for temporal lobe epilepsy","volume":"15","author":"Drion","year":"2018","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.yebeh.2021.108509_b0175","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12974-020-1718-7","article-title":"Decreased expression of Rev-Erbalpha in the epileptic foci of temporal lobe epilepsy and activation of Rev-Erbalpha have anti-inflammatory and neuroprotective effects in the pilocarpine model","volume":"17","author":"Yue","year":"2020","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.yebeh.2021.108509_b0180","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.248344","article-title":"Recent insights into the regulatory networks of NLRP3 inflammasome activation","volume":"133","author":"Weber","year":"2020","journal-title":"J Cell Sci"},{"key":"10.1016\/j.yebeh.2021.108509_b0185","doi-asserted-by":"crossref","first-page":"32145","DOI":"10.1073\/pnas.2009680117","article-title":"The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer's disease","volume":"117","author":"Lonnemann","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.yebeh.2021.108509_b0190","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.phrs.2019.01.035","article-title":"NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia","volume":"142","author":"Ward","year":"2019","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.yebeh.2021.108509_b0195","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12974-014-0212-5","article-title":"Inhibition of the NLRP3 inflammasome provides neuroprotection in rats following amygdala kindling-induced status epilepticus","volume":"11","author":"Meng","year":"2014","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.yebeh.2021.108509_b0200","doi-asserted-by":"crossref","first-page":"856","DOI":"10.3389\/fphar.2019.00856","article-title":"Amentoflavone affects epileptogenesis and exerts neuroprotective effects by inhibiting NLRP3 inflammasome","volume":"10","author":"Rong","year":"2019","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.yebeh.2021.108509_b0205","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1172\/JCI25790","article-title":"Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis","volume":"116","author":"Thimmulappa","year":"2006","journal-title":"J Clin Invest"},{"key":"10.1016\/j.yebeh.2021.108509_b0210","doi-asserted-by":"crossref","DOI":"10.1155\/2008\/725174","article-title":"Disruption of Nrf2 enhances upregulation of nuclear factor-kappaB activity, proinflammatory cytokines, and intercellular adhesion molecule-1 in the brain after traumatic brain injury","volume":"2008","author":"Jin","year":"2008","journal-title":"Mediators Inflamm"},{"key":"10.1016\/j.yebeh.2021.108509_b0215","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12974-020-01863-9","article-title":"Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury","volume":"17","author":"Wang","year":"2020","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.yebeh.2021.108509_b0220","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1089\/ars.2017.7003","article-title":"A dual AMPK\/Nrf2 activator reduces brain inflammation after stroke by enhancing microglia M2 polarization","volume":"28","author":"Wang","year":"2018","journal-title":"Antioxid Redox Signal"},{"key":"10.1016\/j.yebeh.2021.108509_b0225","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20143433","article-title":"Cerebrovascular and neurological disorders: protective role of NRF2","volume":"20","author":"Sivandzade","year":"2019","journal-title":"Int J Mol Sci"}],"container-title":["Epilepsy &amp; Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525505021007708?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525505021007708?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:46:12Z","timestamp":1761504372000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525505021007708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":45,"alternative-id":["S1525505021007708"],"URL":"https:\/\/doi.org\/10.1016\/j.yebeh.2021.108509","relation":{},"ISSN":["1525-5050"],"issn-type":[{"value":"1525-5050","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Klotho alleviates NLRP3 inflammasome-mediated neuroinflammation in a temporal lobe epilepsy rat model by activating the Nrf2 signaling pathway","name":"articletitle","label":"Article Title"},{"value":"Epilepsy & Behavior","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yebeh.2021.108509","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108509"}}