{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T23:40:58Z","timestamp":1763422858805,"version":"3.45.0"},"reference-count":12,"publisher":"Georg Thieme Verlag KG","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study assesses the neuroprotective potential of quercetin in preclinical models of neonatal hypoxic-ischemic brain injury (HIBI) and its role as a possible enhancer of therapeutic hypothermia.<\/jats:p>\n                  <jats:p>A systematic review of 8 preclinical studies was conducted per PRISMA guidelines, sourced from PubMed, Scopus, and Web of Science, with a random-effects meta-analysis.<\/jats:p>\n                  <jats:p>Quercetin significantly lowered infarct volume, seizure susceptibility, and inflammation (pooled standardized mean differences [SMD]\u2009=\u20091.29; 95% confidence interval [CI]: 1.00\u20131.58; p\u2009&lt;\u20090.001). Higher doses (&gt;30\u2009mg\/kg, SMD\u2009=\u20091.65) and intraperitoneal (IP) administration (SMD\u2009=\u20091.42) outperformed lower doses or intravenous (IV) routes (SMD\u2009=\u20090.95). Rat models showed greater benefits (SMD\u2009=\u20091.38) than piglets (SMD\u2009=\u20090.85). Moderate heterogeneity (I\n                  2\u2009=\u200945%) was noted, but sensitivity analysis confirmed robustness (SMD\u2009=\u20091.20). Publication bias was minimal (p\u2009=\u20090.12).<\/jats:p>\n                  <jats:p>Quercetin offers notable neuroprotection in neonatal HIBI, with an optimal 40\u2009mg\/kg IP dose, suggesting it could complement hypothermia. Limited bioavailability and lack of long-term data call for further research in advanced models.<\/jats:p>","DOI":"10.1055\/a-2578-1875","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T19:51:21Z","timestamp":1746042681000},"page":"2203-2208","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of Quercetin in Neonatal Hypoxic-Ischemic Brain Injury: A Meta-analysis"],"prefix":"10.1055","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7810-7105","authenticated-orcid":false,"given":"Ceren","family":"Can","sequence":"additional","affiliation":[{"name":"Department of Pediatric Allergy and Immunology, University of Health Sciences, Bak\u0131rk\u00f6y Dr. Sadi Konuk Training and Research Hospital, Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-7576","authenticated-orcid":false,"given":"\u015eahin","family":"Hamil\u00e7\u0131kan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University of Health Sciences, Ba\u011fc\u0131lar Training and Research Hospital, Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"issue":"22","key":"ref1","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1056\/NEJMoa1112066","article-title":"Childhood outcomes after hypothermia for neonatal encephalopathy","volume":"366","author":"S Shankaran","year":"2012","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"105704","DOI":"10.1016\/j.intimp.2019.105704","article-title":"Quercetin attenuates hypoxia-ischemia induced brain injury in neonatal rats by inhibiting TLR4\/NF-\u03baB signaling pathway","volume":"74","author":"M Wu","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"ref3","first-page":"9467","article-title":"Prediction of outcome methods assessing short- and long-term outcome after therapeutic hypothermia","volume":"13","author":"H Sabir","year":"2023","journal-title":"Sci Rep"},{"issue":"23","key":"ref4","first-page":"5597","article-title":"Antioxidants as a potential therapy against age-related neurodegenerative diseases: amyloid beta toxicity and Alzheimer's disease","volume":"25","author":"L Alvarez-Arellano","year":"2020","journal-title":"Molecules"},{"key":"ref5","first-page":"108436","article-title":"Quercetin stabilizes mitochondrial function and the blood\u2013brain barrier in a rat model of stroke","volume":"83","author":"Y Wang","year":"2020","journal-title":"J Nutr Biochem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.neuint.2015.08.007","article-title":"Intravenous nanosomes of quercetin improve brain function and hemodynamic instability after severe hypoxia in newborn piglets","volume":"89","author":"F Blasina","year":"2015","journal-title":"Neurochem Int"},{"issue":"12","key":"ref7","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s00011-020-01402-5","article-title":"Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation","volume":"69","author":"K Le","year":"2020","journal-title":"Inflamm Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"105064","DOI":"10.1016\/j.neuint.2021.105064","article-title":"Multitarget neuroprotection by quercetin: changes in gene expression in two perinatal asphyxia models","volume":"147","author":"V Cardozo","year":"2021","journal-title":"Neurochem Int"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"791815","DOI":"10.3389\/fped.2022.791815","article-title":"Quercetin administration following hypoxia-induced neonatal brain damage attenuates later-life seizure susceptibility and anxiety-related behavior: modulating inflammatory response","volume":"10","author":"Y Wu","year":"2022","journal-title":"Front Pediatr"},{"issue":"12","key":"ref10","doi-asserted-by":"crossref","first-page":"7649","DOI":"10.1002\/fsn3.3684","article-title":"Protective mechanisms of quercetin in neonatal rat brain injury induced by hypoxic-ischemic brain damage (HIBD)","volume":"11","author":"Y H Xu","year":"2023","journal-title":"Food Sci Nutr"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.brainres.2014.01.035","article-title":"Quercetin improves hypoxia-ischemia induced cognitive deficits via promoting remyelination in neonatal rat","volume":"1553","author":"X Qu","year":"2014","journal-title":"Brain Res"},{"issue":"06","key":"ref12","first-page":"454","article-title":"Effects of quercetin on the learning and memory ability of neonatal rats with hypoxic-ischemic brain damage","volume":"14","author":"J J Huang","year":"2012","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"}],"container-title":["American Journal of Perinatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2578-1875.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T23:36:04Z","timestamp":1763422564000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2578-1875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":12,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,11,17]]},"published-print":{"date-parts":[[2025,12]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2578-1875","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0735-1631","1098-8785"],"issn-type":[{"type":"print","value":"0735-1631"},{"type":"electronic","value":"1098-8785"}],"subject":[],"published":{"date-parts":[[2025,4,30]]}}}