{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:07:14Z","timestamp":1790096834114,"version":"4.0.1"},"reference-count":58,"publisher":"Impact Journals, LLC","issue":"43","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncotarget"],"published-print":{"date-parts":[[2017,9,26]]},"DOI":"10.18632\/oncotarget.20779","type":"journal-article","created":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T22:07:54Z","timestamp":1504908474000},"page":"75308-75325","source":"Crossref","is-referenced-by-count":37,"title":["Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats"],"prefix":"10.18632","volume":"8","author":[{"given":"Mingchu","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijun","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Research, Children\u2019s National Health System, Washington, DC 20010, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7892","published-online":{"date-parts":[[2017,9,8]]},"reference":[{"key":"1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.earlhumdev.2010.05.010","article-title":"Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy","volume":"86","author":"Badawi","year":"2010","journal-title":"Early Hum Dev"},{"key":"2","doi-asserted-by":"publisher","first-page":"609813","DOI":"10.1155\/2011\/609813","article-title":"Perinatal hypoxic-ischemic encephalopathy","volume":"2011","author":"Yang","year":"2011","journal-title":"J Biomed Biotechnol"},{"key":"3","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1001\/jamapediatrics.2014.3269","article-title":"Hypoxic-ischemic encephalopathy: a review for the clinician","volume":"169","author":"Weiss","year":"2015","journal-title":"JAMA Pediatr"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2016.11.001","article-title":"Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy","author":"Lin","year":"2017","journal-title":"Pediatr Neonatol"},{"key":"5","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1056\/NEJMoa1112066","article-title":"Childhood outcomes after hypothermia for neonatal encephalopathy","volume":"366","author":"Tyson","year":"2012","journal-title":"N Engl J Med"},{"key":"6","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/nrneurol.2015.13","article-title":"The role of inflammation in perinatal brain injury","volume":"11","author":"Gressens","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"7","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1097\/01.WCB.0000141559.17620.36","article-title":"Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia","volume":"24","author":"Hagberg","year":"2004","journal-title":"J Cereb Blood Flow Metab"},{"key":"8","doi-asserted-by":"publisher","first-page":"8514","DOI":"10.1073\/pnas.1432609100","article-title":"Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway","volume":"100","author":"Vartanian","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"9","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.braindev.2014.12.001","article-title":"Cerebral hypoxia-ischemia increases toll-like receptor 2 and 4 expression in the hippocampus of neonatal rats","volume":"37","author":"Sun","year":"2015","journal-title":"Brain Dev"},{"key":"10","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1742-2094-10-23","article-title":"Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia","volume":"10","author":"Ling","year":"2013","journal-title":"J Neuroinflammation"},{"key":"11","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/nm.3407","article-title":"Development, maintenance and disruption of the blood-brain barrier","volume":"19","author":"Ransohoff","year":"2013","journal-title":"Nat Med"},{"key":"12","doi-asserted-by":"publisher","first-page":"S58","DOI":"10.1212\/WNL.0b013e3182695836","article-title":"Role of the vascular endothelium and plaque in acute ischemic stroke","volume":"79","author":"Madden","year":"2012","journal-title":"Neurology"},{"key":"13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1742-2094-8-40","article-title":"Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation","volume":"8","author":"Ho","year":"2011","journal-title":"J Neuroinflammation"},{"key":"14","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/ana.22419","article-title":"Neuronal cell death in neonatal hypoxia-ischemia","volume":"69","author":"Martin","year":"2011","journal-title":"Ann Neurol"},{"key":"15","doi-asserted-by":"publisher","first-page":"4901014","DOI":"10.1155\/2016\/4901014","article-title":"Plasticity in the neonatal brain following hypoxic-ischaemic injury","volume":"2016","author":"Hristova","year":"2016","journal-title":"Neural Plast"},{"key":"16","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1056\/NEJMra041996","article-title":"Neonatal brain injury","volume":"351","author":"Ferriero","year":"2004","journal-title":"N Engl J Med"},{"key":"17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.brainresrev.2005.07.003","article-title":"Apoptosis in perinatal hypoxic-ischemic brain injury: how important is it and should it be inhibited?","volume":"50","author":"Martin","year":"2005","journal-title":"Brain Res Brain Res Rev"},{"key":"18","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1038\/ncomms3192","article-title":"Metformin improves healthspan and lifespan in mice","volume":"4","author":"Zhang","year":"2013","journal-title":"Nat Commun"},{"key":"19","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1073\/pnas.1417636112","article-title":"Immune-mediated antitumor effect by type 2 diabetes drug, metformin","volume":"112","author":"Udono","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"20","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s11011-014-9632-2","article-title":"Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia","volume":"30","author":"Sarkaki","year":"2015","journal-title":"Metab Brain Dis"},{"key":"21","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.bbrc.2016.05.148","article-title":"Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury","volume":"477","author":"Mei","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00210-009-0477-x","article-title":"Metformin increases phagocytosis and acidifies lysosomal\/endosomal compartments in AMPK-dependent manner in rat primary microglia","volume":"381","author":"Okopien","year":"2010","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"23","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s12974-014-0177-4","article-title":"Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion","volume":"11","author":"Yang","year":"2014","journal-title":"J Neuroinflammation"},{"key":"24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.physbeh.2016.12.021","article-title":"Metformin protects the brain against ischemia\/reperfusion injury through PI3K\/Akt1\/JNK3 signaling pathways in rats","volume":"170","author":"Yu","year":"2017","journal-title":"Physiol Behav"},{"key":"25","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1007\/s12035-016-9895-1","article-title":"Metformin improves functional recovery after spinal cord injury via autophagy flux stimulation","volume":"54","author":"Wang","year":"2017","journal-title":"Mol Neurobiol"},{"key":"26","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.bbrc.2013.03.036","article-title":"Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells","volume":"433","author":"Kataoka","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.bbi.2014.03.003","article-title":"Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia\/macrophages and increased angiogenesis and neurogenesis following experimental stroke","volume":"40","author":"Zhen","year":"2014","journal-title":"Brain Behav Immun"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0459-8","article-title":"Metformin attenuates cognitive impairments in hypoxia-ischemia neonatal rats via improving remyelination","author":"Yang","year":"2016","journal-title":"Cell Mol Neurobiol"},{"key":"29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0847-6","article-title":"Brain microvascular pericytes in health and disease","volume":"122","author":"Yemisci","year":"2011","journal-title":"Acta Neuropathol"},{"key":"30","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nn.4288","article-title":"Pericytes of the neurovascular unit: key functions and signaling pathways","volume":"19","author":"Zlokovic","year":"2016","journal-title":"Nat Neurosci"},{"key":"31","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.nbd.2009.12.010","article-title":"Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms","volume":"37","author":"Chen","year":"2010","journal-title":"Neurobiol Dis"},{"key":"32","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Brocklehurst","year":"2009","journal-title":"N Engl J Med"},{"key":"33","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/jcbfm.2014.41","article-title":"Mechanisms of perinatal arterial ischemic stroke","volume":"34","author":"Vexler","year":"2014","journal-title":"J Cereb Blood Flow Metab"},{"key":"34","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.stemcr.2015.06.011","article-title":"Activating endogenous neural precursor cells using metformin leads to neural repair and functional recovery in a model of childhood brain injury","volume":"5","author":"Morshead","year":"2015","journal-title":"Stem Cell Reports"},{"key":"35","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/aps.2013.89","article-title":"Inflammatory responses in hypoxic ischemic encephalopathy","volume":"34","author":"McCullough","year":"2013","journal-title":"Acta Pharmacol Sin"},{"key":"36","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.pediatrneurol.2008.09.016","article-title":"Role of perinatal inflammation in cerebral palsy","volume":"40","author":"Sebire","year":"2009","journal-title":"Pediatr Neurol"},{"key":"37","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/pr.2015.47","article-title":"Hypoxic postconditioning reduces microglial activation, astrocyte and caspase activity, and inflammatory markers after hypoxia-ischemia in the neonatal rat brain","volume":"77","author":"Jones","year":"2015","journal-title":"Pediatr Res"},{"key":"38","doi-asserted-by":"publisher","first-page":"632592","DOI":"10.1155\/2015\/632592","article-title":"Hypoxic preconditioning suppresses glial activation and neuroinflammation in neonatal brain insults","volume":"2015","author":"Fu","year":"2015","journal-title":"Mediators Inflamm"},{"key":"39","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.intimp.2016.10.025","article-title":"Peroxiredoxin 1-mediated activation of TLR4\/NF-kappaB pathway contributes to neuroinflammatory injury in intracerebral hemorrhage","volume":"41","author":"Du","year":"2016","journal-title":"Int Immunopharmacol"},{"key":"40","doi-asserted-by":"publisher","first-page":"2816056","DOI":"10.1155\/2016\/2816056","article-title":"Daphnetin protects against cerebral ischemia\/reperfusion injury in mice via inhibition of TLR4\/NF-\u03baB signaling pathway","volume":"2016","author":"Wang","year":"2016","journal-title":"Biomed Res Int"},{"key":"41","doi-asserted-by":"publisher","first-page":"13798","DOI":"10.1073\/pnas.0702553104","article-title":"Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits","volume":"104","author":"Mattson","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"42","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.bbrc.2006.12.057","article-title":"Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice","volume":"353","author":"Wang","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"43","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1161\/STROKEAHA.109.560250","article-title":"Alternate pathways preserve tumor necrosis factor-alpha production after nuclear factor-kappaB inhibition in neonatal cerebral hypoxia-ischemia","volume":"40","author":"Kavelaars","year":"2009","journal-title":"Stroke"},{"key":"44","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.nbd.2010.01.016","article-title":"NF-kappa B inhibition after neonatal cerebral hypoxia-ischemia improves long-term motor and cognitive outcome in rats","volume":"38","author":"Kavelaars","year":"2010","journal-title":"Neurobiol Dis"},{"key":"45","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1177\/0022034510381264","article-title":"TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk","volume":"90","author":"Martin","year":"2011","journal-title":"J Dent Res"},{"key":"46","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/ana.23648","article-title":"The blood-brain barrier in health and disease","volume":"72","author":"Daneman","year":"2012","journal-title":"Ann Neurol"},{"key":"47","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1161\/STROKEAHA.110.608257","article-title":"Blood-brain barrier breakdown in acute and chronic cerebrovascular disease","volume":"42","author":"Rosenberg","year":"2011","journal-title":"Stroke"},{"key":"48","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/jcbfm.2014.255","article-title":"Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia","volume":"35","author":"Mallard","year":"2015","journal-title":"J Cereb Blood Flow Metab"},{"key":"49","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.nbd.2016.02.020","article-title":"Omega-3 polyunsaturated fatty acids mitigate blood-brain barrier disruption after hypoxic-ischemic brain injury","volume":"91","author":"Gao","year":"2016","journal-title":"Neurobiol Dis"},{"key":"50","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.expneurol.2014.12.020","article-title":"G-CSF attenuates neuroinflammation and stabilizes the blood-brain barrier via the PI3K\/Akt\/GSK-3\u03b2 signaling pathway following neonatal hypoxia-ischemia in rats","volume":"272","author":"Tang","year":"2015","journal-title":"Exp Neurol"},{"key":"51","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature09513","article-title":"Pericytes are required for blood-brain barrier integrity during embryogenesis","volume":"468","author":"Barres","year":"2010","journal-title":"Nature"},{"key":"52","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes regulate the blood-brain barrier","volume":"468","author":"Betsholtz","year":"2010","journal-title":"Nature"},{"key":"53","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/sj.cdd.4401545","article-title":"The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia","volume":"12","author":"Blomgren","year":"2005","journal-title":"Cell Death Differ"},{"key":"54","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00204-014-1448-7","article-title":"The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update","volume":"89","author":"Ahsan","year":"2015","journal-title":"Arch Toxicol"},{"key":"55","doi-asserted-by":"publisher","first-page":"506320","DOI":"10.1155\/2012\/506320","article-title":"Molecular mechanisms of neonatal brain injury","volume":"2012","author":"Hagberg","year":"2012","journal-title":"Neurol Res Int"},{"key":"56","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1002\/(SICI)1097-4547(19990115)55:2<158::AID-JNR3>3.0.CO;2-1","article-title":"Rat model of perinatal hypoxic-ischemic brain damage","volume":"55","author":"Vannucci","year":"1999","journal-title":"J Neurosci Res"},{"key":"57","doi-asserted-by":"publisher","first-page":"15988","DOI":"10.1074\/jbc.M112.428789","article-title":"Mechanisms of neuroprotection from hypoxia-ischemia (HI) brain injury by up-regulation of cytoglobin (CYGB) in a neonatal rat model","volume":"288","author":"Shi","year":"2013","journal-title":"J Biol Chem"},{"key":"58","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0006-8993(96)00122-9","article-title":"Mild postischemic hypothermia limits cerebral injury following transient focal ischemia in rat neocortex","volume":"718","author":"Lee","year":"1996","journal-title":"Brain Res"}],"container-title":["Oncotarget"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.20779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T11:56:42Z","timestamp":1589198202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.20779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,8]]},"references-count":58,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2017,9,26]]}},"alternative-id":["20779","29088867"],"URL":"https:\/\/doi.org\/10.18632\/oncotarget.20779","relation":{},"ISSN":["1949-2553"],"issn-type":[{"value":"1949-2553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,8]]}}}