{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:12:42Z","timestamp":1783937562324,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2013\/07559-3"],"award-info":[{"award-number":["2013\/07559-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2019\/00213-0"],"award-info":[{"award-number":["2019\/00213-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2019\/00048-0"],"award-info":[{"award-number":["2019\/00048-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2019\/25948-3"],"award-info":[{"award-number":["2019\/25948-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2021\/04441-8"],"award-info":[{"award-number":["2021\/04441-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2017\/26167-0"],"award-info":[{"award-number":["2017\/26167-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["2021\/04451-3"],"award-info":[{"award-number":["2021\/04451-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","doi-asserted-by":"publisher","award":["311923\/2019-4"],"award-info":[{"award-number":["311923\/2019-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2013\/07559-3"],"award-info":[{"award-number":["2013\/07559-3"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2019\/00213-0"],"award-info":[{"award-number":["2019\/00213-0"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2019\/00048-0"],"award-info":[{"award-number":["2019\/00048-0"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2019\/25948-3"],"award-info":[{"award-number":["2019\/25948-3"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2021\/04441-8"],"award-info":[{"award-number":["2021\/04441-8"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2017\/26167-0"],"award-info":[{"award-number":["2017\/26167-0"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["2021\/04451-3"],"award-info":[{"award-number":["2021\/04451-3"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","award":["311923\/2019-4"],"award-info":[{"award-number":["311923\/2019-4"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2013\/07559-3"],"award-info":[{"award-number":["2013\/07559-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2019\/00213-0"],"award-info":[{"award-number":["2019\/00213-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2019\/00048-0"],"award-info":[{"award-number":["2019\/00048-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2019\/25948-3"],"award-info":[{"award-number":["2019\/25948-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2021\/04441-8"],"award-info":[{"award-number":["2021\/04441-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2017\/26167-0"],"award-info":[{"award-number":["2017\/26167-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["2021\/04451-3"],"award-info":[{"award-number":["2021\/04451-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Pesquisa","doi-asserted-by":"publisher","award":["311923\/2019-4"],"award-info":[{"award-number":["311923\/2019-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of disease in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM for a supplementary and preliminary comparison: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We analyzed the group of patients and controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), \u03b2-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p &lt; 0.05). In addition, we found some suggestive metabolites (without enough predictability) by multivariate analysis (VIP scores &gt; 2), such as lipoproteins, lactate, glucose, unsaturated lipids, isoleucine, and proline, that might be relevant to the process of pharmacoresistance in the comparison between patients with refractory and responsive MTLE. The identified metabolites for the comparison between MTLE patients and controls were linked to different biological pathways related to cell-energy metabolism and pathways related to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In conclusion, in addition to insights into the mechanisms underlying MTLE, our results suggest that plasma metabolites may be used as disease biomarkers. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.<\/jats:p>","DOI":"10.3390\/metabo12050446","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T04:04:19Z","timestamp":1652760259000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-7913","authenticated-orcid":false,"given":"Alexandre B.","family":"Godoi","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-8351","authenticated-orcid":false,"given":"Amanda M.","family":"do Canto","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Donatti","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-334X","authenticated-orcid":false,"given":"Danielle C. F.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina K.","family":"Alvim","sequence":"additional","affiliation":[{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"},{"name":"Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa L.","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"},{"name":"Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-5169","authenticated-orcid":false,"given":"Lucas G.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2645-7418","authenticated-orcid":false,"given":"Melissa","family":"Quintero","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-7332","authenticated-orcid":false,"given":"Ljubica","family":"Tasic","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9336-9568","authenticated-orcid":false,"given":"Fernando","family":"Cendes","sequence":"additional","affiliation":[{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"},{"name":"Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6221-6822","authenticated-orcid":false,"given":"Iscia","family":"Lopes-Cendes","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-888, Brazil"},{"name":"Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas 13083-888, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000503831","article-title":"The epidemiology of epilepsy","volume":"54","author":"Beghi","year":"2020","journal-title":"Neuroepidemiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"Scheffer","year":"2017","journal-title":"Epilepsia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00401-014-1292-0","article-title":"Epilepsies associated with hippocampal sclerosis","volume":"128","author":"Cendes","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1177\/107385840100700410","article-title":"Mesial temporal lobe epilepsy: What have we learned?","volume":"7","author":"Engel","year":"2001","journal-title":"Neuroscientist"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/epi.12550","article-title":"ILAE Official Report: A practical clinical definition of epilepsy","volume":"55","author":"Fisher","year":"2014","journal-title":"Epilepsia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1212\/WNL.51.5.1256","article-title":"Is the underlying cause of epilepsy a major prognostic factor for recurrence?","volume":"51","author":"Semah","year":"1998","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/epi.13368","article-title":"Epilepsy diagnostic and treatment needs identified with a collaborative database involving tertiary centers in France","volume":"57","author":"Chipaux","year":"2016","journal-title":"Epilepsia"},{"key":"ref_8","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":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.yebeh.2014.05.031","article-title":"The consequences of refractory epilepsy and its treatment","volume":"37","author":"Laxer","year":"2014","journal-title":"Epilepsy Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3171\/2019.4.JNS183235","article-title":"A historical cohort of temporal lobe surgery for medically refractory epilepsy: A systematic review and meta-analysis to guide future nonrandomized controlled trial studies","volume":"133","author":"Lee","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_11","first-page":"1044","article-title":"Temporopolar amygdalohippocampectomy: Seizure control and postoperative outcomes","volume":"134","author":"Ayub","year":"2020","journal-title":"J. Neurosurg."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bruxel, E.M., Canto, A.M.D., Bruno, D.C.F., Geraldis, J.C., and Lopes-Cendes, I. (2021). Multi-omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy. Epilepsia Open.","DOI":"10.1002\/epi4.12536"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Stanisic, D., Martins, L.G., and Tasic, L. (2022). Nuclear magnetic resonance spectroscopy in analyses of biological samples. Tools and Trends in Bioanalytical Chemistry, Springer.","DOI":"10.1007\/978-3-030-82381-8_9"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1007\/s11306-013-0524-y","article-title":"NMR-based metabolomics in human disease diagnosis: Applications, limitations, and recommendations","volume":"9","author":"Emwas","year":"2013","journal-title":"Metabolomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2174\/138620712802650522","article-title":"Application of NMR metabolomics to search for human disease biomarkers","volume":"15","author":"Gebregiworgis","year":"2012","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3389\/fneur.2017.00459","article-title":"Metabolomics as a tool for the characterization of drug-resistant epilepsy","volume":"8","author":"Murgia","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Deutch, A.Y., and Roth, R.H. (2014). Pharmacology and biochemistry of synaptic transmission. From Molecules to Networks, Academic Press.","DOI":"10.1016\/B978-0-12-397179-1.00007-5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1007\/s00018-007-7332-3","article-title":"The regulation of ion channels and transporters by glycolytically derived ATP","volume":"64","author":"Malester","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/glia.23247","article-title":"Epilepsy and astrocyte energy metabolism","volume":"66","author":"Boison","year":"2017","journal-title":"Glia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.pharmthera.2014.06.001","article-title":"Epilepsy, energy deficiency and new therapeutic approaches including diet","volume":"144","author":"Reid","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15035","DOI":"10.1038\/s41598-019-51337-z","article-title":"NMR-based metabolomics in pediatric drug resistant epilepsy\u2014Preliminary results","volume":"9","author":"Boguszewicz","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_22","unstructured":"McGuire, K., and Beerman, K.A. (2007). Nutritional Sciences: From Fundamentals to Food, Thomson\/Wadsworth."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-3-0348-8393-1_9","article-title":"Peroxisome proliferator activated receptor agonists","volume":"Volume 89","year":"2000","journal-title":"New Approaches to Drug Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H1060","DOI":"10.1152\/ajpheart.00646.2012","article-title":"Ketone body metabolism and cardiovascular disease","volume":"304","author":"Cotter","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/978-1-4614-4989-8_51","article-title":"Contribution of brain glucose and ketone bodies to oxidative metabolism","volume":"Volume 765","author":"Welch","year":"2013","journal-title":"Oxygen Transport to Tissue XXXIV"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nbd.2015.05.013","article-title":"Potent anti-seizure effects of D-leucine","volume":"82","author":"Hartman","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1177\/0883073809336295","article-title":"Branched chain amino acids as adjunctive therapy to ketogenic diet in epilepsy: Pilot study and hypothesis","volume":"24","author":"Evangeliou","year":"2009","journal-title":"J. Child Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/ANA.0000000000000499","article-title":"Effects of branched-chain amino acid supplementation on spontaneous seizures and neuronal viability in a model of mesial temporal lobe epilepsy","volume":"31","author":"Gruenbaum","year":"2019","journal-title":"J. Neurosurg. Anesthesiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0168-0102(01)00232-2","article-title":"Modulation of absence seizures by branched-chain amino acids: Correlation with brain amino acid concentrations","volume":"40","author":"Dufour","year":"2001","journal-title":"Neurosci. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0091-3057(94)90504-5","article-title":"Effects of valine, leucine, isoleucine, and a balanced amino acid solution on the seizure threshold to picrotoxin in rats","volume":"48","author":"Skeie","year":"1994","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.biopsych.2009.01.003","article-title":"A risk PRODH haplotype affects sensorimotor gating, memory, schizotypy, and anxiety in healthy male subjects","volume":"65","author":"Roussos","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ajhg.2015.03.003","article-title":"Mutations in PYCR2, encoding pyrroline-5-carboxylate reductase 2, cause microcephaly and hypomyelination","volume":"96","author":"Nakayama","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/s10038-018-0478-z","article-title":"The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy","volume":"63","author":"Yin","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.diabres.2018.03.020","article-title":"A population-based study of epilepsy incidence in association with type 2 diabetes and severe hypoglycaemia","volume":"140","author":"Lu","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.seizure.2016.03.002","article-title":"Metabolic syndrome in young adults with epilepsy","volume":"37","author":"Nair","year":"2016","journal-title":"Seizure"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.yebeh.2006.02.008","article-title":"Insulin-related metabolic changes during treatment with valproate in patients with epilepsy","volume":"8","author":"Pakarinen","year":"2006","journal-title":"Epilepsy Behav."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/ana.20727","article-title":"An association between type 1 diabetes and idiopathic generalized epilepsy","volume":"59","author":"McCorry","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1038\/s41598-020-61401-8","article-title":"Laser microdissection-based microproteomics of the hippocampus of a rat epilepsy model reveals regional differences in protein abundances","volume":"10","author":"Canto","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/hipo.23268","article-title":"Multi-omics analysis suggests enhanced epileptogenesis in the Cornu ammonis 3 of the pilocarpine model of mesial temporal lobe epilepsy","volume":"31","author":"Canto","year":"2020","journal-title":"Hippocampus"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22416","DOI":"10.1038\/srep22416","article-title":"RNA sequencing reveals region-specific molecular mechanisms associated with epileptogenesis in a model of classical hippocampal sclerosis","volume":"6","author":"Vieira","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1021\/acs.chemrestox.1c00335","article-title":"Toxicometabolomics and biotransformation product elucidation in single zebrafish embryos exposed to carbamazepine from environmentally-relevant to morphologically altering doses","volume":"35","author":"Ribbenstedt","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"131793","DOI":"10.1016\/j.chemosphere.2021.131793","article-title":"An integrated metabolomics and proteogenomics approach reveals molecular alterations following carbamazepine exposure in the male mussel Mytilus galloprovincialis","volume":"286","author":"Dumas","year":"2022","journal-title":"Chemosphere"},{"key":"ref_43","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":"Thom","year":"2013","journal-title":"Epilepsia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1212\/WNL.0b013e3181d76b72","article-title":"Relationship between environmental factors and gray matter atrophy in refractory MTLE","volume":"74","author":"Yasuda","year":"2010","journal-title":"Neurology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.seizure.2005.10.005","article-title":"Comparison of short-term outcome between surgical and clinical treatment in temporal lobe epilepsy: A prospective study","volume":"15","author":"Yasuda","year":"2006","journal-title":"Seizure"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_47","unstructured":"Wishart, D.S., Feunang, Y.D., Marcu, A., Guo, A.C., Liang, K., V\u00e1zquez-Fresno, R., Sajed, T., Johnson, D., Li, C., and Karu, N. (2022, March 15). HMDB 4.0: The Human Metabolome Database for 2018. Available online: http:\/\/www.hmdb.ca\/."},{"key":"ref_48","unstructured":"Ulrich, E.L., Akutsu, H., Doreleijers, J.F., Harano, Y., Ioannidis, Y.E., Lin, J., Livny, M., Mading, S., Maziuk, D., and Miller, Z. (2022, March 25). BioMagResBank. Available online: http:\/\/www.bmrb.wisc.edu\/."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/bioinformatics\/btr661","article-title":"Metscape 2 bioinformatics tool for the analysis and visualization of metabolomics and gene expression data","volume":"28","author":"Karnovsky","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkp1002","article-title":"SMPDB: The small molecule pathway database","volume":"38","author":"Frolkis","year":"2010","journal-title":"Nucleic Acids Res."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/446\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:11:37Z","timestamp":1760137897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["metabo12050446"],"URL":"https:\/\/doi.org\/10.3390\/metabo12050446","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202203.0314.v1","asserted-by":"object"}]},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]}}}