{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:38:07Z","timestamp":1780666687412,"version":"3.54.1"},"reference-count":105,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T00:00:00Z","timestamp":1478304000000},"content-version":"am","delay-in-days":370,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006402","name":"ALS Therapy Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmn.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Discovery Today"],"published-print":{"date-parts":[[2015,11]]},"DOI":"10.1016\/j.drudis.2015.09.001","type":"journal-article","created":{"date-parts":[[2015,9,7]],"date-time":"2015-09-07T02:18:26Z","timestamp":1441592306000},"page":"1372-1381","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":53,"title":["Neuroprotective agents for neonatal hypoxic\u2013ischemic brain injury"],"prefix":"10.1016","volume":"20","author":[{"given":"Qiaofeng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharati","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyang","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Manning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanhu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne A.","family":"Kroessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiemin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry E.","family":"Inder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.drudis.2015.09.001_bib0530","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1467-7687.2006.00499.x","article-title":"Brain and cognitive-behavioural development after asphyxia at term birth","volume":"9","author":"De Haan","year":"2006","journal-title":"Dev. Sci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0535","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/ana.23647","article-title":"Neonatal encephalopathy: an inadequate term for hypoxic\u2013ischemic encephalopathy","volume":"72","author":"Volpe","year":"2012","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0540","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1056\/NEJMcps050929","article-title":"Whole-body hypothermia for neonates with hypoxic\u2013ischemic encephalopathy","volume":"353","author":"Shankaran","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.drudis.2015.09.001_bib0545","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.drudis.2015.09.001_bib0550","doi-asserted-by":"crossref","first-page":"e624","DOI":"10.1542\/peds.2014-1566","article-title":"Cognitive outcomes after neonatal encephalopathy","volume":"135","author":"Pappas","year":"2015","journal-title":"Pediatrics"},{"key":"10.1016\/j.drudis.2015.09.001_bib0555","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jpeds.2004.07.034","article-title":"Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic\u2013ischemic encephalopathy","volume":"145","author":"Inder","year":"2004","journal-title":"J. Pediatr."},{"key":"10.1016\/j.drudis.2015.09.001_bib0560","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.2174\/156652412803833517","article-title":"Therapeutic hypothermia as a neuroprotective strategy in neonatal hypoxic\u2013ischemic brain injury and traumatic brain injury","volume":"12","author":"Ma","year":"2012","journal-title":"Curr. Mol. Med."},{"key":"10.1016\/j.drudis.2015.09.001_bib0565","doi-asserted-by":"crossref","first-page":"c363","DOI":"10.1136\/bmj.c363","article-title":"Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data","volume":"340","author":"Edwards","year":"2010","journal-title":"BMJ"},{"key":"10.1016\/j.drudis.2015.09.001_bib0570","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fnins.2014.00040","article-title":"The mechanisms and treatment of asphyxial encephalopathy","volume":"8","author":"Wassink","year":"2014","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0575","doi-asserted-by":"crossref","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":"10.1016\/j.drudis.2015.09.001_bib0580","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.yebeh.2005.05.015","article-title":"Molecular mediators of hypoxic\u2013ischemic injury and implications for epilepsy in the developing brain","volume":"7","author":"Hossain","year":"2005","journal-title":"Epilepsy Behav."},{"key":"10.1016\/j.drudis.2015.09.001_bib0585","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ana.22419","article-title":"Neuronal cell death in neonatal hypoxia\u2013ischemia","volume":"69","author":"Northington","year":"2011","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0590","series-title":"Neurodegeneration: Theory, Disorders and Treatments","first-page":"125","article-title":"Targeting caspases in neonatal hypoxia\u2013ischemic brain injury and traumatic brain injury","author":"Wang","year":"2011"},{"key":"10.1016\/j.drudis.2015.09.001_bib0595","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/ana.20547","article-title":"Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia","volume":"58","author":"Ma","year":"2005","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0600","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/sj.jcbfm.9600184","article-title":"Xenon preconditioning reduces brain damage from neonatal asphyxia in rats","volume":"26","author":"Ma","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.drudis.2015.09.001_bib0605","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/ana.22016","article-title":"Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs","volume":"68","author":"Chakkarapani","year":"2010","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0610","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/jcbfm.2013.123","article-title":"Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic\u2013ischemic pig model","volume":"33","author":"Chakkarapani","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.drudis.2015.09.001_bib0615","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1681\/ASN.2008070712","article-title":"Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1alpha activation","volume":"20","author":"Ma","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0620","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1542\/peds.2013-0787","article-title":"Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study","volume":"133","author":"Dingley","year":"2014","journal-title":"Pediatrics"},{"key":"10.1016\/j.drudis.2015.09.001_bib0625","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1161\/STROKEAHA.108.540765","article-title":"Methazolamide and melatonin inhibit mitochondrial cytochrome C release and are neuroprotective in experimental models of ischemic injury","volume":"40","author":"Wang","year":"2009","journal-title":"Stroke"},{"key":"10.1016\/j.drudis.2015.09.001_bib0630","doi-asserted-by":"crossref","first-page":"14496","DOI":"10.1523\/JNEUROSCI.3059-11.2011","article-title":"The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity","volume":"31","author":"Wang","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0635","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1755-5949.2009.00105.x","article-title":"The antiapoptotic activity of melatonin in neurodegenerative diseases","volume":"15","author":"Wang","year":"2009","journal-title":"CNS Neurosci. Ther."},{"key":"10.1016\/j.drudis.2015.09.001_bib0640","first-page":"1033","article-title":"The antiapoptotic effects of melatonin in neonatal hypoxic\u2013ischemic brain injury and adult ischemic stroke","volume":"2","author":"Wang","year":"2014","journal-title":"J. Neurosurg. Spine"},{"key":"10.1016\/j.drudis.2015.09.001_bib0645","doi-asserted-by":"crossref","first-page":"9379","DOI":"10.3390\/ijms14059379","article-title":"Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia\u2013ischemia","volume":"14","author":"Alonso-Alconada","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0650","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1600-079X.2007.00503.x","article-title":"Melatonin protects from the long-term consequences of a neonatal hypoxic\u2013ischemic brain injury in rats","volume":"44","author":"Carloni","year":"2008","journal-title":"J. Pineal. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0655","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/jpi.12156","article-title":"Melatonin reduces endoplasmic reticulum stress and preserves sirtuin 1 expression in neuronal cells of newborn rats after hypoxia\u2013ischemia","volume":"57","author":"Carloni","year":"2014","journal-title":"J. Pineal. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0660","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1159\/000232562","article-title":"Neuroprotective properties of melatonin in a model of birth asphyxia in the spiny mouse (Acomyscahirinus)","volume":"31","author":"Hutton","year":"2009","journal-title":"Dev. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0665","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1600-079X.2008.00639.x","article-title":"Free iron, total F-isoprostanes and total F-neuroprostanes in a model of neonatal hypoxic\u2013ischemic encephalopathy: neuroprotective effect of melatonin","volume":"46","author":"Signorini","year":"2009","journal-title":"J. Pineal. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0670","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.braindev.2006.05.007","article-title":"The effect of melatonin on protein oxidation and nitric oxide in the brain tissue of hypoxic neonatal rats","volume":"29","author":"Eskiocak","year":"2007","journal-title":"Brain Dev."},{"key":"10.1016\/j.drudis.2015.09.001_bib0675","first-page":"435","article-title":"Neuroprotective effects of melatonin administered alone or in combination with topiramate in neonatal hypoxic\u2013ischemic rat model","volume":"30","author":"Ozyener","year":"2012","journal-title":"Restor. Neurol. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0680","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/brain\/aws285","article-title":"Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model","volume":"136","author":"Robertson","year":"2013","journal-title":"Brain"},{"key":"10.1016\/j.drudis.2015.09.001_bib0685","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1034\/j.1600-079X.2001.310409.x","article-title":"Increased levels of malondialdehyde and nitrite\/nitrate in the blood of asphyxiated newborns: reduction by melatonin","volume":"31","author":"Fulia","year":"2001","journal-title":"J. Pineal. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0690","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1600-079X.2008.00649.x","article-title":"Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin","volume":"46","author":"Gitto","year":"2009","journal-title":"J. Pineal. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0695","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/jp.2014.186","article-title":"Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study","volume":"35","author":"Aly","year":"2015","journal-title":"J. Perinatol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0700","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/bcp.12092","article-title":"Pharmacokinetics of melatonin in preterm infants","volume":"76","author":"Merchant","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0705","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1161\/01.STR.0000173406.04891.8c","article-title":"Neonatal hypoxia\/ischemia is associated with decreased inflammatory mediators after erythropoietin administration","volume":"36","author":"Sun","year":"2005","journal-title":"Stroke"},{"key":"10.1016\/j.drudis.2015.09.001_bib0710","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000089951","article-title":"Erythropoietin downregulates bax and DP5 proapoptotic gene expression in neonatal hypoxic\u2013ischemic brain injury","volume":"89","author":"Kumral","year":"2006","journal-title":"Biol. Neonate"},{"key":"10.1016\/j.drudis.2015.09.001_bib0715","doi-asserted-by":"crossref","first-page":"898","DOI":"10.3345\/kjp.2010.53.10.898","article-title":"The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic\u2013ischemic brain injury in neonatal rats","volume":"53","author":"Kim","year":"2010","journal-title":"Korean J. Pediatr."},{"key":"10.1016\/j.drudis.2015.09.001_bib0720","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/path.2862","article-title":"Erythropoietin protects against apoptosis and increases expression of non-neuronal cell markers in the hypoxia-injured developing brain","volume":"224","author":"Yamada","year":"2011","journal-title":"J. Pathol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0725","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.nbd.2003.10.006","article-title":"Erythropoietin protects the developing brain against N-methyl-D-aspartate receptor antagonist neurotoxicity","volume":"15","author":"Dzietko","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.drudis.2015.09.001_bib0730","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000080490","article-title":"Erythropoietin increases glutathione peroxidase enzyme activity and decreases lipid peroxidation levels in hypoxic\u2013ischemic brain injury in neonatal rats","volume":"87","author":"Kumral","year":"2005","journal-title":"Biol. Neonate"},{"key":"10.1016\/j.drudis.2015.09.001_bib0735","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1542\/peds.2012-0498","article-title":"Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics","volume":"130","author":"Wu","year":"2012","journal-title":"Pediatrics"},{"key":"10.1016\/j.drudis.2015.09.001_bib0740","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1542\/peds.2009-2268","article-title":"Human recombinant erythropoietin in asphyxia neonatorum: pilot trial","volume":"125","author":"Elmahdy","year":"2010","journal-title":"Pediatrics"},{"key":"10.1016\/j.drudis.2015.09.001_bib0745","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1542\/peds.2008-3553","article-title":"Erythropoietin improved neurologic outcomes in newborns with hypoxic\u2013ischemic encephalopathy","volume":"124","author":"Zhu","year":"2009","journal-title":"Pediatrics"},{"key":"10.1016\/j.drudis.2015.09.001_bib0750","doi-asserted-by":"crossref","first-page":"9733","DOI":"10.1523\/JNEUROSCI.21-24-09733.2001","article-title":"Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells","volume":"21","author":"Shingo","year":"2001","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0755","first-page":"279","article-title":"Expression of erythropoietin receptor mRNA in mouse brain hemispheres","volume":"43","author":"Poveshchenko","year":"2001","journal-title":"Tsitologiia"},{"key":"10.1016\/j.drudis.2015.09.001_bib0760","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/npp.2009.115","article-title":"Normal development of brain circuits","volume":"35","author":"Tau","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.drudis.2015.09.001_bib0765","first-page":"405","article-title":"Allopurinol administered after inducing hypoxia\u2013ischemia reduces brain injury in 7-day-old rats","volume":"33","author":"Palmer","year":"1993","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0770","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.brainres.2005.11.061","article-title":"Effect of allopurinol on brain adenosine levels during hypoxia in newborn piglets","volume":"1073-1074","author":"Marro","year":"2006","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0775","first-page":"Cd006817","article-title":"Allopurinol for preventing mortality and morbidity in newborn infants with hypoxic\u2013ischaemic encephalopathy","volume":"7","author":"Chaudhari","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.drudis.2015.09.001_bib0780","doi-asserted-by":"crossref","first-page":"F163","DOI":"10.1136\/adc.2005.086652","article-title":"Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia","volume":"91","author":"Benders","year":"2006","journal-title":"Arch. Dis. Child Fetal Neonatal Ed."},{"key":"10.1016\/j.drudis.2015.09.001_bib0785","doi-asserted-by":"crossref","first-page":"F216","DOI":"10.1136\/archdischild-2014-306769","article-title":"Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial","volume":"100","author":"Kaandorp","year":"2015","journal-title":"Arch. Dis. Child Fetal Neonatal Ed."},{"key":"10.1016\/j.drudis.2015.09.001_bib0790","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0006-8993(02)03395-4","article-title":"Magnesium pre-treatment reduces neuronal apoptosis in newborn rats in hypoxia\u2013ischemia","volume":"955","author":"Canan","year":"2002","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0795","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000151753","article-title":"Evaluation of long-lasting sensorimotor consequences following neonatal hypoxic\u2013ischemic brain injury in rats: the neuroprotective role of MgSO4","volume":"95","author":"Pazaiti","year":"2009","journal-title":"Neonatology"},{"key":"10.1016\/j.drudis.2015.09.001_bib0800","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1159\/000320643","article-title":"Possible neuroprotective effects of magnesium sulfate and melatonin as both pre- and post-treatment in a neonatal hypoxic\u2013ischemic rat model","volume":"99","author":"Cetinkaya","year":"2011","journal-title":"Neonatology"},{"key":"10.1016\/j.drudis.2015.09.001_bib0805","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000362206","article-title":"Magnesium is not consistently neuroprotective for perinatal hypoxia\u2013ischemia in term-equivalent models in preclinical studies: a systematic review","volume":"36","author":"Galinsky","year":"2014","journal-title":"Dev. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0810","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/jp.2013.65","article-title":"Magnesium for newborns with hypoxic\u2013ischemic encephalopathy: a systematic review and meta-analysis","volume":"33","author":"Tagin","year":"2013","journal-title":"J. Perinatol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0815","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1523\/JNEUROSCI.0477-04.2004","article-title":"Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate","volume":"24","author":"Follett","year":"2004","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0820","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.expneurol.2006.04.038","article-title":"Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats","volume":"201","author":"Noh","year":"2006","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0825","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.brainres.2005.07.061","article-title":"Neuroprotective effects of topiramate after hypoxia\u2013ischemia in newborn piglets","volume":"1058","author":"Schubert","year":"2005","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0830","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/1471-2431-12-144","article-title":"Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)","volume":"12","author":"Filippi","year":"2012","journal-title":"BMC Pediatr."},{"key":"10.1016\/j.drudis.2015.09.001_bib0835","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.1523\/JNEUROSCI.1702-08.2008","article-title":"NMDA receptor blockade with memantine attenuates white matter injury in a rat model of periventricular leukomalacia","volume":"28","author":"Manning","year":"2008","journal-title":"J. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0840","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.ijdevneu.2011.05.005","article-title":"The clinically available NMDA receptor antagonist, memantine, exhibits relative safety in the developing rat brain","volume":"29","author":"Manning","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0845","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.expneurol.2013.01.015","article-title":"Intranasal delivery of cell-penetrating anti-NF-(B peptides (Tat-NBD) alleviates infection-sensitized hypoxic\u2013ischemic brain injury","volume":"247","author":"Yang","year":"2013","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0850","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1203\/01.pdr.0000196807.10122.5f","article-title":"Selective inhibition of nuclear factor-kappaB activation after hypoxia\/ischemia in neonatal rats is not neuroprotective","volume":"59","author":"Van den Tweel","year":"2006","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0855","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1161\/STROKEAHA.108.516401","article-title":"A dual role of the NF-kappaB pathway in neonatal hypoxic\u2013ischemic brain damage","volume":"39","author":"Nijboer","year":"2008","journal-title":"Stroke"},{"key":"10.1016\/j.drudis.2015.09.001_bib0860","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1161\/STROKEAHA.107.504175","article-title":"Strong neuroprotection by inhibition of NF-kappaB after neonatal hypoxia\u2013ischemia involves apoptotic mechanisms but is independent of cytokines","volume":"39","author":"Nijboer","year":"2008","journal-title":"Stroke"},{"key":"10.1016\/j.drudis.2015.09.001_bib0865","doi-asserted-by":"crossref","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\u2013ischemia","volume":"40","author":"Nijboer","year":"2009","journal-title":"Stroke"},{"key":"10.1016\/j.drudis.2015.09.001_bib0870","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1016\/j.freeradbiomed.2006.01.011","article-title":"Antioxidant pyrrolidinedithiocarbamate activates Akt-GSK signaling and is neuroprotective in neonatal hypoxia\u2013ischemia","volume":"40","author":"Nurmi","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.drudis.2015.09.001_bib0875","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/ana.24087","article-title":"Innate defense regulator peptide 1018 protects against perinatal brain injury","volume":"75","author":"Bolouri","year":"2014","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0880","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/sj.jcbfm.9600007","article-title":"Long-term neuroprotection with 2-iminobiotin, an inhibitor of neuronal and inducible nitric oxide synthase, after cerebral hypoxia\u2013ischemia in neonatal rats","volume":"25","author":"van den Tweel","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.drudis.2015.09.001_bib0885","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/sj.jcbfm.9600342","article-title":"Gender-specific neuroprotection by 2-iminobiotin after hypoxia\u2013ischemia in the neonatal rat via a nitric oxide independent pathway","volume":"27","author":"Nijboer","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.drudis.2015.09.001_bib0890","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1471-4159.2004.02500.x","article-title":"Nitrosylation precedes caspase-3 activation and translocation of apoptosis-inducing factor in neonatal rat cerebral hypoxia\u2013ischaemia","volume":"90","author":"Zhu","year":"2004","journal-title":"J. Neurochem."},{"key":"10.1016\/j.drudis.2015.09.001_bib0895","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.pbb.2012.02.020","article-title":"Selective and nonselective neuronal NOS inhibitors impair cognitive function in the three panel runway and passive avoidance tasks in rats","volume":"101","author":"Utkan","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.drudis.2015.09.001_bib0900","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1203\/00006450-200001000-00015","article-title":"Protective effect of aminoguanidine on hypoxic\u2013ischemic brain damage and temporal profile of brain nitric oxide in neonatal rat","volume":"47","author":"Tsuji","year":"2000","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0905","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s11064-005-5978-5","article-title":"Neuroprotective effects of indomethacin and aminoguanidine in the newborn rats with hypoxic\u2013ischemic cerebral injury","volume":"30","author":"Tutak","year":"2005","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0910","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.brainres.2009.07.010","article-title":"The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic\u2013ischemic cerebral injury","volume":"1289","author":"Taskin","year":"2009","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0915","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1159\/000327244","article-title":"Neuronal nitric oxide synthase inhibition prevents cerebral palsy following hypoxia\u2013ischemia in fetal rabbits: comparison between JI-8 and 7-nitroindazole","volume":"33","author":"Yu","year":"2011","journal-title":"Dev. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0920","doi-asserted-by":"crossref","first-page":"H1809","DOI":"10.1152\/ajpheart.00301.2007","article-title":"Perivascular nitric oxide and superoxide in neonatal cerebral hypoxia\u2013ischemia","volume":"295","author":"Fabian","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0925","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1159\/000069044","article-title":"Inhibition of nNOS and iNOS following hypoxia\u2013ischaemia improves long-term outcome but does not influence the inflammatory response in the neonatal rat brain","volume":"24","author":"Van den Tweel","year":"2002","journal-title":"Dev. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0930","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.neuro.2005.03.009","article-title":"Neuroprotective effect of simvastatin in stroke: a comparison between adult and neonatal rat models of cerebral ischemia","volume":"26","author":"Cimino","year":"2005","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.drudis.2015.09.001_bib0935","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.nbd.2011.04.021","article-title":"Hypoxic-preconditioning induces neuroprotection against hypoxia\u2013ischemia in newborn piglet brain","volume":"43","author":"Ara","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.drudis.2015.09.001_bib0940","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1006\/exnr.2000.7492","article-title":"BDNF protects against spatial memory deficits following neonatal hypoxia\u2013ischemia","volume":"166","author":"Almli","year":"2000","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib0945","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.3923\/pjbs.2009.1498.1504","article-title":"Cord blood brain derived neurotrophic factor: diagnostic and prognostic marker in full term newborns with perinatal asphyxia","volume":"12","author":"Imam","year":"2009","journal-title":"Pak. J. Biol. Sci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0950","doi-asserted-by":"crossref","first-page":"e88962","DOI":"10.1371\/journal.pone.0088962","article-title":"TrkB agonist antibody pretreatment enhances neuronal survival and long-term sensory motor function following hypoxic ischemic injury in neonatal rats","volume":"9","author":"Kim","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.drudis.2015.09.001_bib0955","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.brainres.2005.09.042","article-title":"IGF-1 protects oligodendrocyte progenitor cells and improves neurological functions following cerebral hypoxia\u2013ischemia in the neonatal rat","volume":"1063","author":"Lin","year":"2005","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0960","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1159\/000105471","article-title":"Delayed IGF-1 administration rescues oligodendrocyte progenitors from glutamate-induced cell death and hypoxic\u2013ischemic brain damage","volume":"29","author":"Wood","year":"2007","journal-title":"Dev. Neurosci."},{"key":"10.1016\/j.drudis.2015.09.001_bib0965","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1179\/174313208X338133","article-title":"Delayed IGF-1 treatment reduced long-term hypoxia\u2013ischemia-induced brain damage and improved behavior recovery of immature rats","volume":"31","author":"Zhong","year":"2009","journal-title":"Neurol. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib0970","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/jcbfm.1993.27","article-title":"Basic fibroblast growth factor protects against hypoxia\u2013ischemia and NMDA neurotoxicity in neonatal rats","volume":"13","author":"Nozaki","year":"1993","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.drudis.2015.09.001_bib0975","first-page":"235","article-title":"Effect of basic fibral growth factor on nestin expression in neonatal rats following hypoxic\u2013ischemic brain damage","volume":"8","author":"Peng","year":"2006","journal-title":"Zhongguo Dang Daierkezazhi"},{"key":"10.1016\/j.drudis.2015.09.001_bib0980","first-page":"354","article-title":"Neuroprotective effects of exogenous basic fibroblast growth factor on the hypoxic\u2013ischemic brain damage of neonatal rats","volume":"45","author":"Sun","year":"2007","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"10.1016\/j.drudis.2015.09.001_bib0985","first-page":"856","article-title":"Effect of basic fibroblast growth factor on expression of protein and mRNA of bone morphogenetic protein 4 in hypoxic\u2013ischemic brain damage in newborn rats","volume":"47","author":"Yin","year":"2009","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"10.1016\/j.drudis.2015.09.001_bib0990","doi-asserted-by":"crossref","DOI":"10.1042\/AN20090002","article-title":"Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF","author":"Alagappan","year":"2009","journal-title":"ASN. Neuro."},{"key":"10.1016\/j.drudis.2015.09.001_bib0995","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00381-013-2304-4","article-title":"Stem cells for brain repair in neonatal hypoxia\u2013ischemia","volume":"30","author":"Chicha","year":"2014","journal-title":"Childs Nerv. Syst."},{"key":"10.1016\/j.drudis.2015.09.001_bib1000","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.brainres.2014.02.019","article-title":"Umbilical cord blood cells regulate the differentiation of endogenous neural stem cells in hypoxic ischemic neonatal rats via the hedgehog signaling pathway","volume":"1560","author":"Wang","year":"2014","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1005","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.brainres.2013.04.038","article-title":"Umbilical cord blood cells regulate endogenous neural stem cell proliferation via hedgehog signaling in hypoxic ischemic neonatal rats","volume":"1518","author":"Wang","year":"2013","journal-title":"Brain Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1010","first-page":"419","article-title":"Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage","volume":"68","author":"van Velthoven","year":"2010","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1015","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/exnr.2001.7853","article-title":"Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats","volume":"174","author":"Zhao","year":"2002","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.drudis.2015.09.001_bib1020","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jpeds.2013.11.036","article-title":"Feasibility of autologous cord blood cells for infants with hypoxic\u2013ischemic encephalopathy","volume":"164","author":"Cotten","year":"2014","journal-title":"J. Pediatr."},{"key":"10.1016\/j.drudis.2015.09.001_bib1025","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1203\/PDR.0b013e3181fcbef3","article-title":"Beneficial effect of erythropoietin on sensorimotor function and white matter after hypoxia\u2013ischemia in neonatal mice","volume":"69","author":"Fan","year":"2011","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1030","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1161\/STROKEAHA.111.000104","article-title":"Erythropoietin increases neurogenesis and oligodendrogliosis of subventricular zone precursor cells after neonatal stroke","volume":"44","author":"Gonzalez","year":"2013","journal-title":"Stroke"},{"key":"10.1016\/j.drudis.2015.09.001_bib1035","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/pr.2013.155","article-title":"Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic\u2013ischemic brain injury","volume":"74","author":"Jantzie","year":"2013","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1040","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/pr.2012.139","article-title":"Hypothermia and erythropoietin for neuroprotection after neonatal brain damage","volume":"73","author":"Fan","year":"2013","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1045","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/pr.2012.138","article-title":"Effects of combination therapy using hypothermia and erythropoietin in a rat model of neonatal hypoxia\u2013ischemia","volume":"73","author":"Fang","year":"2013","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.drudis.2015.09.001_bib1050","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.jpeds.2011.12.052","article-title":"Which neuroprotective agents are ready for bench to bedside translation in the newborn infant?","volume":"160","author":"Robertson","year":"2012","journal-title":"J. Pediatr."}],"container-title":["Drug Discovery Today"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644615003414?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644615003414?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:24:24Z","timestamp":1761222264000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1359644615003414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11]]},"references-count":105,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["S1359644615003414"],"URL":"https:\/\/doi.org\/10.1016\/j.drudis.2015.09.001","relation":{},"ISSN":["1359-6446"],"issn-type":[{"value":"1359-6446","type":"print"}],"subject":[],"published":{"date-parts":[[2015,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neuroprotective agents for neonatal hypoxic\u2013ischemic brain injury","name":"articletitle","label":"Article Title"},{"value":"Drug Discovery Today","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.drudis.2015.09.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}