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Hypoxic\u2013ischemic encephalopathy (HIE) is the most common cause of brain injury and seizures in term neonates. The goal of this study was to describe HCAR1 expression and function in the neonatal brain and understand its role in HIE\u2010associated seizures. HCAR1 expression was measured using quantitative reverse transcriptase polymerase chain reaction in postnatal day (p)10\u201350 mice. Neuronal properties and spontaneous excitatory postsynaptic currents (sEPSCs) were measured in hippocampal principal neurons from HCAR1 knockout and wild\u2010type mice when exposed to lactate. p10 HCAR1 knockout and wild\u2010type mice were exposed to hypoxia\u2013ischemia (HI) and underwent electroencephalography to compare seizure burden. HCAR1 was expressed at p10 at similar levels to adults. Lactate decreased amplitudes and sEPSC frequency in wild\u2010type but not HCAR1 knockout mice. After HI, HCAR1 knockout mice had higher seizure burden and behavioral seizure scores than wild\u2010type mice. HCAR1 is expressed on neurons and plays a role in neuronal excitability and seizures in the neonatal brain.<\/jats:p>","DOI":"10.1002\/epi.70172","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:02:01Z","timestamp":1772985721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactate receptor\n                    <scp>HCAR1<\/scp>\n                    in neonatal hypoxic\u2013ischemic seizures"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1902-1499","authenticated-orcid":false,"given":"Jennifer","family":"Burnsed","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-6909","authenticated-orcid":false,"given":"Angelina","family":"June","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4285-612X","authenticated-orcid":false,"given":"Maria","family":"Marlicz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmy","family":"Zucker","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie","family":"Kain\u2010Kuzniewski","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Mulhern","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Maharaj","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6429-7846","authenticated-orcid":false,"given":"Chengsan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-2061","authenticated-orcid":false,"given":"Suchitra","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-1352","authenticated-orcid":false,"given":"Jaideep","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Neuroscience University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"The Human Protein Atlas [Internet]. Available from:https:\/\/www.proteinatlas.org\/ENSG00000196917\u2010HCAR1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221080324"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2092-18.2019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221077499"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76451"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22958"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac419"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071721"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2020.09.006"},{"key":"e_1_2_9_11_1","first-page":"1","article-title":"Hydroxycarboxylic acid receptor 2 mediates \u03b2\u2010hydroxybutyrate's antiseizure effect in mice","author":"Naderi S","year":"2025","journal-title":"Ann Neurol"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.12.009"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_9_14_1","first-page":"1","article-title":"Increased glutamatergic synaptic transmission during development in layer II\/III mouse motor cortex pyramidal neurons","volume":"33","author":"Burnsed J","year":"2022","journal-title":"Cereb Cortex"},{"issue":"160","key":"e_1_2_9_15_1","first-page":"1","article-title":"Continuous video electroencephalogram during hypoxia\u2010ischemia in neonatal mice","volume":"2020","author":"Wagley PK","year":"2020","journal-title":"J Vis Exp"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00173"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25601"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.100800"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00293"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jp.7211023"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-020-04645-z"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-025-06979-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109679"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20908355"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70172","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:26:18Z","timestamp":1776097578000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/epi.70172"],"URL":"https:\/\/doi.org\/10.1002\/epi.70172","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"assertion":[{"value":"2025-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}