{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:46:52Z","timestamp":1793479612224,"version":"4.5.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.ejphar.2023.175933","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T01:28:22Z","timestamp":1689902902000},"page":"175933","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Ketogenic diet and \u03b2-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway"],"prefix":"10.1016","volume":"955","author":[{"given":"Chuman","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjia","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengren","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaibin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyue","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2023.175933_bib1","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1161\/STROKEAHA.118.020586","article-title":"Imaging the effects of beta-hydroxybutyrate on peri-infarct neurovascular function and metabolism","volume":"49","author":"Bazzigaluppi","year":"2018","journal-title":"Stroke"},{"key":"10.1016\/j.ejphar.2023.175933_bib2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21062111","article-title":"Environmental signals on microglial function during brain development, neuroplasticity, and disease","volume":"21","author":"Chagas","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2023.175933_bib3","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.2174\/1570159X19666210729123137","article-title":"The potential role of hypoxia-inducible factor-1 in the progression and therapy of central nervous system diseases","volume":"20","author":"Chen","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.ejphar.2023.175933_bib4","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1161\/ATVBAHA.112.300310","article-title":"Endogenous IRAK-M attenuates postinfarction remodeling through effects on macrophages and fibroblasts","volume":"32","author":"Chen","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.ejphar.2023.175933_bib5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s00281-022-00943-7","article-title":"Inflammatory responses after ischemic stroke","volume":"44","author":"DeLong","year":"2022","journal-title":"Semin. Immunopathol."},{"key":"10.1016\/j.ejphar.2023.175933_bib6","first-page":"2532","article-title":"Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M","volume":"116","author":"Deng","year":"2006","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2023.175933_bib7","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1161\/STROKEAHA.116.014091","article-title":"Inhibition of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 reduces ischemic brain damage in mice","volume":"47","author":"Denorme","year":"2016","journal-title":"Stroke"},{"key":"10.1016\/j.ejphar.2023.175933_bib8","doi-asserted-by":"crossref","DOI":"10.3390\/nu14235003","article-title":"The role of ketogenic diet in the treatment of neurological diseases","volume":"14","author":"Dynka","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.ejphar.2023.175933_bib9","doi-asserted-by":"crossref","DOI":"10.1007\/s12035-023-03325-8","article-title":"The ketogenic diet but not hydroxycitric acid keeps brain mitochondria quality control and mtDNA integrity under focal stroke","author":"Gureev","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.ejphar.2023.175933_bib10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.neuroscience.2019.06.009","article-title":"The impact of the ketogenic diet on glial cells morphology. A quantitative morphological analysis","volume":"413","author":"Gzielo","year":"2019","journal-title":"Neuroscience"},{"key":"10.1016\/j.ejphar.2023.175933_bib11","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24054334","article-title":"Neuroprotective strategies for ischemic stroke-future perspectives","volume":"24","author":"Haupt","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2023.175933_bib12","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.801985","article-title":"Biological functions and regulatory mechanisms of hypoxia-inducible factor-1alpha in ischemic stroke","volume":"12","author":"He","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2023.175933_bib13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3389\/fnagi.2018.00391","article-title":"A ketogenic diet improves cognition and has biochemical effects in prefrontal cortex that are dissociable from Hippocampus","volume":"10","author":"Hernandez","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.ejphar.2023.175933_bib14","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/glia.23241","article-title":"The ketone body metabolite beta-hydroxybutyrate induces an antidepression-associated ramification of microglia via HDACs inhibition-triggered Akt-small RhoGTPase activation","volume":"66","author":"Huang","year":"2018","journal-title":"Glia"},{"key":"10.1016\/j.ejphar.2023.175933_bib15","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1152\/physrev.00011.2010","article-title":"Physiology of microglia","volume":"91","author":"Kettenmann","year":"2011","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejphar.2023.175933_bib16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuron.2012.12.023","article-title":"Microglia: new roles for the synaptic stripper","volume":"77","author":"Kettenmann","year":"2013","journal-title":"Neuron"},{"key":"10.1016\/j.ejphar.2023.175933_bib17","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0092-8674(02)00827-9","article-title":"IRAK-M is a negative regulator of Toll-like receptor signaling","volume":"110","author":"Kobayashi","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2023.175933_bib18","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1007\/s11064-022-03637-6","article-title":"Ss-hydroxybutyrate improves mitochondrial function after transient ischemia in the mouse","volume":"47","author":"Lehto","year":"2022","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.ejphar.2023.175933_bib19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jaut.2019.04.020","article-title":"Interleukin-1 receptor associated kinase (IRAK)-M -mediated type 2 microglia polarization ameliorates the severity of experimental autoimmune encephalomyelitis (EAE)","volume":"102","author":"Liu","year":"2019","journal-title":"J. Autoimmun."},{"key":"10.1016\/j.ejphar.2023.175933_bib20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neulet.2018.06.016","article-title":"Ketogenic diet attenuates oxidative stress and inflammation after spinal cord injury by activating Nrf2 and suppressing the NF-kappaB signaling pathways","volume":"683","author":"Lu","year":"2018","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.ejphar.2023.175933_bib21","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3389\/fncel.2018.00504","article-title":"IRAK-M deficiency exacerbates ischemic neurovascular injuries in experimental stroke mice","volume":"12","author":"Lyu","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.ejphar.2023.175933_bib22","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/6742427","article-title":"Anti-inflammatory strategy for M2 microglial polarization using retinoic acid-loaded nanoparticles","volume":"2017","author":"Machado-Pereira","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.ejphar.2023.175933_bib23","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21186454","article-title":"Neuroinflammatory mechanisms in ischemic stroke: focus on cardioembolic stroke, background, and therapeutic approaches","volume":"21","author":"Maida","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2023.175933_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2020.113317","article-title":"Differential glucose and beta-hydroxybutyrate metabolism confers an intrinsic neuroprotection to the immature brain in a rat model of neonatal hypoxia ischemia","volume":"330","author":"Odorcyk","year":"2020","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.ejphar.2023.175933_bib25","doi-asserted-by":"crossref","DOI":"10.3390\/antiox7050063","article-title":"Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer's disease","volume":"7","author":"Pinto","year":"2018","journal-title":"Antioxidants"},{"key":"10.1016\/j.ejphar.2023.175933_bib26","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24043102","article-title":"The ketogenic diet and neuroinflammation: the action of beta-hydroxybutyrate in a microglial cell line","volume":"24","author":"Polito","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2023.175933_bib27","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1038\/jcbfm.2008.79","article-title":"Neuroprotection in diet-induced ketotic rat brain after focal ischemia","volume":"28","author":"Puchowicz","year":"2008","journal-title":"J. Cerebr. Blood Flow Metabol."},{"key":"10.1016\/j.ejphar.2023.175933_bib28","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1038\/ncomms4944","article-title":"The beta-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages","volume":"5","author":"Rahman","year":"2014","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejphar.2023.175933_bib29","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2022.947567","article-title":"Ketogenic diets and Ketone suplementation: a strategy for therapeutic intervention","volume":"9","author":"Saris","year":"2022","journal-title":"Front. Nutr."},{"key":"10.1016\/j.ejphar.2023.175933_bib30","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.4049\/jimmunol.0901709","article-title":"Critical role of IL-1 receptor-associated kinase-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia","volume":"184","author":"Seki","year":"2010","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejphar.2023.175933_bib31","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.immuni.2015.02.001","article-title":"Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1alpha","volume":"42","author":"Shalova","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.ejphar.2023.175933_bib32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12866-017-1095-2","article-title":"IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis","volume":"17","author":"Shen","year":"2017","journal-title":"BMC Microbiol."},{"key":"10.1016\/j.ejphar.2023.175933_bib33","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202216269","article-title":"Systemic inflammation after stroke: implications for post-stroke comorbidities","volume":"14","author":"Simats","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ejphar.2023.175933_bib34","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1038\/onc.2010.619","article-title":"TGF-beta-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth","volume":"30","author":"Standiford","year":"2011","journal-title":"Oncogene"},{"key":"10.1016\/j.ejphar.2023.175933_bib35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1254\/jjp.89.36","article-title":"Beta-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia","volume":"89","author":"Suzuki","year":"2002","journal-title":"Jpn. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2023.175933_bib36","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1254\/jjp.87.143","article-title":"Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats","volume":"87","author":"Suzuki","year":"2001","journal-title":"Jpn. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2023.175933_bib37","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1474-4422(18)30500-3","article-title":"Stroke in China: advances and challenges in epidemiology, prevention, and management","volume":"18","author":"Wu","year":"2019","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.ejphar.2023.175933_bib38","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-1-4419-1241-1_9","article-title":"Diet-induced ketosis improves cognitive performance in aged rats","volume":"662","author":"Xu","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.ejphar.2023.175933_bib39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-3-319-55231-6_28","article-title":"Diet-induced ketosis protects against focal cerebral ischemia in mouse","volume":"977","author":"Xu","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.ejphar.2023.175933_bib40","doi-asserted-by":"crossref","first-page":"6229","DOI":"10.1007\/s00253-021-11482-w","article-title":"On the nutritional and therapeutic effects of ketone body D-beta-hydroxybutyrate","volume":"105","author":"Yao","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.ejphar.2023.175933_bib41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s12017-011-8145-y","article-title":"Energy restriction negates NMDA receptor antagonist efficacy in ischemic stroke","volume":"13","author":"Yoon","year":"2011","journal-title":"NeuroMolecular Med."},{"key":"10.1016\/j.ejphar.2023.175933_bib42","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm.3804","article-title":"The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease","volume":"21","author":"Youm","year":"2015","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejphar.2023.175933_bib43","doi-asserted-by":"crossref","DOI":"10.3390\/nu12092616","article-title":"Therapeutic use of the ketogenic diet in refractory epilepsy: what we know and what still needs to Be learned","volume":"12","author":"Zarnowska","year":"2020","journal-title":"Nutrients"},{"key":"10.1016\/j.ejphar.2023.175933_bib44","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.1172\/JCI121901","article-title":"TLR-stimulated IRAKM activates caspase-8 inflammasome in microglia and promotes neuroinflammation","volume":"128","author":"Zhang","year":"2018","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2023.175933_bib45","doi-asserted-by":"crossref","first-page":"7611","DOI":"10.1074\/jbc.274.12.7611","article-title":"Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes","volume":"274","author":"Zhang","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2023.175933_bib46","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/emboj.2013.2","article-title":"IRAK-M mediates Toll-like receptor\/IL-1R-induced NFkappaB activation and cytokine production","volume":"32","author":"Zhou","year":"2013","journal-title":"EMBO J."},{"key":"10.1016\/j.ejphar.2023.175933_bib47","doi-asserted-by":"crossref","DOI":"10.1111\/bpa.13006","article-title":"Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke","volume":"32","author":"Zhu","year":"2022","journal-title":"Brain Pathol."},{"key":"10.1016\/j.ejphar.2023.175933_bib48","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1097\/NEN.0000000000000118","article-title":"Hypoxia-inducible factor 1alpha mediates neuroprotection of hypoxic postconditioning against global cerebral ischemia","volume":"73","author":"Zhu","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299923004454?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299923004454?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T14:20:48Z","timestamp":1736346048000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299923004454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":48,"alternative-id":["S0014299923004454"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2023.175933","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ketogenic diet and \u03b2-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2023.175933","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"175933"}}