{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T04:44:30Z","timestamp":1783831470566,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy with early childhood onset. Patients with DS do not respond well to antiepileptic drugs and have only a few treatment options available. Here, we evaluated the effect of medium chain triglyceride (MCT) diet therapy in a mouse model of DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Scn1a<\/jats:italic><jats:sup>R1407X\/+<\/jats:sup> DS mice were given diets supplemented with MCTs with varying ratios of decanoic (C10) and octanoic (C8) acid or a control diet for 4\u00a0weeks. Video monitoring was performed to evaluate spontaneous convulsive seizure frequency. Susceptibility to hyperthermia\u2010induced seizures was also examined. Medium chain fatty acids, and mitochondrial and antioxidant markers were assessed in brain homogenate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dietary intervention with MCTs significantly prolonged survival and reduced convulsive seizure frequency during the critical period of highest seizure occurrence in the <jats:italic>Scn1a<\/jats:italic><jats:sup>R1407X\/+<\/jats:sup> DS mice. Moreover, MCT diet therapy showed protective effects against hyperthermia\u2010induced seizures. We demonstrated that coadministration of C10\/C8 was effective at reducing both seizures and mortality, whereas C10 alone only reduced mortality, suggesting that the ratio of C10 to C8 in the MCT is an important factor for efficacy. When C10 and C8 are supplemented at an 80:20 ratio in the diet, C10 accumulates in the brain in high enough concentrations to enhance brain energy metabolism by both stimulating mitochondrial enrichment and increasing its antioxidant status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The results from this study indicate that MCT diet therapy may provide therapeutic benefits in DS. Future clinical studies would elucidate whether these positive effects are mirrored in human patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17101","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T06:59:45Z","timestamp":1635490785000},"page":"3131-3142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Protective effects of medium chain triglyceride diet in a mouse model of Dravet syndrome"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2143-3265","authenticated-orcid":false,"given":"Nikola","family":"Jancovski","sequence":"first","affiliation":[{"name":"Florey Institute for Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer University College London Great Ormond Street Institute of Child Health London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Orford","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer University College London Great Ormond Street Institute of Child Health London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody","family":"Li","sequence":"additional","affiliation":[{"name":"Florey Institute for Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Davis","family":"Jones","sequence":"additional","affiliation":[{"name":"Florey Institute for Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisseth Estefania","family":"Burbano","sequence":"additional","affiliation":[{"name":"Florey Institute for Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Vitaflo International Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Reid","sequence":"additional","affiliation":[{"name":"Florey Institute for Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Heales","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism, Chemical Pathology, University College London Metabolism, Great Ormond Street for Children Hospital Chemical Pathology Great Ormond Street Hospital London UK"},{"name":"Neurometabolic Unit National Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Eaton","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer University College London Great Ormond Street Institute of Child Health London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Petrou","sequence":"additional","affiliation":[{"name":"Florey Institute for Neuroscience and Mental Health University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-1807"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.02994.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21083"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5270-06.2007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804764115"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03007.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.01.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01870.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16334"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118702772.ch9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.07.023"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb00115.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12646"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9930-4"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv325"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13833"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150095"},{"key":"e_1_2_9_19_1","first-page":"e1310","article-title":"Vita\u00ae: a feasibility study of a blend of medium chain triglycerides to manage drug\u2010resistant epilepsy","volume":"136","author":"Schoeler N","year":"2021","journal-title":"Brain Commun"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105009"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(77)90043-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1989.tb09150.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.09.009"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182872867"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2007.02.001"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(00)00145-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05460.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026107405399"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12225"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30408-8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpn.12030"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9060631"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00278"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.12.015"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2014.10.013"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.294785"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1988.tb02958.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07245.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.00915.x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0008-16.2016"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16976"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20899"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200011)48:5<766::AID-ANA10>3.0.CO;2-M"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2009.11.011"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2013.01.004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01821.x"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.4103\/0972-2327.144008"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17101","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.17101","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T09:42:52Z","timestamp":1693215772000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,28]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1111\/epi.17101"],"URL":"https:\/\/doi.org\/10.1111\/epi.17101","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,28]]},"assertion":[{"value":"2021-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}