{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:26:42Z","timestamp":1786966002474,"version":"build-2736575974"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality worldwide. While the application of therapeutic hypothermia has improved neurodevelopmental outcomes for some survivors of HIE, this lone treatment option is only available to a subset of affected neonates. Src kinase, an enzyme central to the apoptotic cascade, is a potential pharmacologic target to preserve typical brain development after HIE. Here, we present evidence of the neuroprotective effects of targeting Src kinase in preclinical models of HIE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a comprehensive literature search using the National Library of Medicine's MEDLINE database to compile studies examining the impact of Src kinase regulation on neurodevelopment in animal models. Each eligible study was assessed for bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty studies met the inclusion criteria, and most studies had an intermediate risk for bias. Together, these studies showed that targeting Src kinase resulted in a neuroprotective effect as assessed by neuropathology, enzymatic activity, and neurobehavioral outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Src kinase is an effective neuroprotective target in the setting of acute hypoxic injury. Src kinase inhibition triggers multiple signaling pathways of the sub-membranous focal adhesions and the nucleus, resulting in modulation of calcium signaling and prevention of cell death. Despite the significant heterogeneity of the research studies that we examined, the available evidence can serve as proof-of-concept for further studies on this promising therapeutic strategy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2022.1049655","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T11:44:04Z","timestamp":1669290244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuroprotective effect of Src kinase in hypoxia-ischemia: A systematic review"],"prefix":"10.3389","volume":"16","author":[{"given":"Panagiotis","family":"Christidis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhya","family":"Vij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatios","family":"Petousis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javid","family":"Ghaemmaghami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhairav V.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Koutroulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Kratimenos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1097\/WNR.0000000000000835","article-title":"Effects of Src kinase inhibition on expression of pro-caspase-2 after brain hypoxia in a piglet animal model","volume":"28","author":"Angelis","year":"","journal-title":"NeuroReport."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/2810295","article-title":"Effects of Src kinase inhibition on expression of protein tyrosine phosphatase 1b after brain hypoxia in a piglet animal model","volume":"2017","author":"Angelis","year":"","journal-title":"Mediat. Inflam."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1007\/s11064-015-1717-8","article-title":"Temporal changes in caspase-1 and caspase-8 activities following brain hypoxia with and without src kinase inhibition in a piglet animal model","volume":"40","author":"Angelis","year":"2015","journal-title":"Neurochem. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1007\/s11064-014-1404-1","article-title":"The role of src kinase in the caspase-1 pathway after hypoxia in the brain of newborn piglets","volume":"39","author":"Angelis","year":"2014","journal-title":"Neurochem. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s00018-003-3319-x","article-title":"Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury","volume":"61","author":"Arundine","year":"2004","journal-title":"Cell. Molec. Life Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"34543","DOI":"10.1074\/jbc.274.49.34543","article-title":"Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B","volume":"274","author":"Barrett","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.brainres.2006.04.119","article-title":"Hypoxic\/Ischemic models in newborn piglet: Comparison of constant FiO2 versus variable FiO2 delivery","volume":"1100","author":"Bj\u00f6rkman","year":"2006","journal-title":"Brain Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"33241","DOI":"10.1074\/jbc.M113.512087","article-title":"Proapoptotic Bax and Bak proteins form stable protein-permeable pores of tunable size","volume":"288","author":"Bleicken","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/pr.2013.203","article-title":"Estimates of neonatal morbidities and disabilities at regional and global levels for 2010: introduction, methods overview and relevant findings from the Global Burden of Disease study","volume":"74","author":"Blencowe","year":"2013","journal-title":"Pediatr. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S1097-2765(03)00051-0","article-title":"A unified model for apical caspase activation","volume":"11","author":"Boatright","year":"2003","journal-title":"Molec. Cell"},{"key":"B11","first-page":"653","article-title":"Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal cerebral ischemic\/reperfusion injury","volume":"288","author":"Bochelen","year":"1999","journal-title":"J. Pharmacol. Exper. Therap."},{"key":"B12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0304-3940(02)01439-8","article-title":"Tyrosine kinase and tyrosine phosphatase participate in regulation of interactions of NMDA receptor subunit 2A with Src and Fyn mediated by PSD-95 after transient brain ischemia","volume":"339","author":"Chen","year":"2003","journal-title":"Neurosci. Lett."},{"key":"B13","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.siny.2010.02.002","article-title":"Synergistic neuroprotective therapies with hypothermia","volume":"15","author":"Cilio","year":"2010","journal-title":"Semin. Fetal. Neonatal. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.neuro.2007.01.014","article-title":"Extrapolating brain development from experimental species to humans","volume":"28","author":"Clancy","year":"2007","journal-title":"NeuroToxicol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ebm2.7","article-title":"A protocol format for the preparation, registration and publication of systematic reviews of animal intervention studies","volume":"2","author":"De Vries","year":"2015","journal-title":"Evidence-based Preclin. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.neulet.2012.06.029","article-title":"Mechanism of caspase-9 activation during hypoxia in the cerebral cortex of newborn piglets: The role of Src kinase","volume":"523","author":"Delivoria-Papadopoulos","year":"2012","journal-title":"Neurosci. Lett."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1007\/s11064-007-9301-5","article-title":"Differential expression of apoptotic proteins following hypoxia-induced CREB phosphorylation in the cerebral cortex of newborn piglets","volume":"32","author":"Delivoria-Papadopoulos","year":"2007","journal-title":"Neurochem. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1007\/s11064-011-0477-3","article-title":"Mechanism of CaM kinase IV activation during hypoxia in neuronal nuclei of the cerebral cortex of newborn piglets: The role of Src kinase","volume":"36","author":"Delivoria-Papadopoulos","year":"2011","journal-title":"Neurochem. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1007\/978-3-319-29489-6_272","article-title":"Biochemical Basis of Hypoxic-Ischemic Encephalopathy","volume":"11","author":"Delivoria-Papadopoulos","year":"2018","journal-title":"Neonatology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/dmcn.12727","article-title":"The long-term health, social, and financial burden of hypoxic-ischaemic encephalopathy","volume":"57","author":"Eunson","year":"2015","journal-title":"Develop. Med. Child Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.jpeds.2005.11.015","article-title":"Neonatal hypoglycemia and occipital cerebral injury","volume":"148","author":"Filan","year":"2006","journal-title":"J. Pediatrics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.neures.2004.06.013","article-title":"Mechanisms of oxygen glucose deprivation-induced glutamate release from cerebrocortical slice cultures","volume":"50","author":"Fujimoto","year":"2004","journal-title":"Neurosci. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.nurx.2006.01.007","article-title":"Hypothermic neuroprotection","volume":"3","author":"Gunn","year":"2006","journal-title":"NeuroRX"},{"key":"B24","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.neuroscience.2006.08.031","article-title":"Sustained activation of Src-family tyrosine kinases by ischemia: A potential mechanism mediating extracellular signal-regulated kinase cascades in hippocampal dentate gyrus","volume":"143","author":"Guo","year":"2006","journal-title":"Neuroscience"},{"key":"B25","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1203\/00006450-199704000-00009","article-title":"Posthypoxic Hypothermia in Newborn Piglets","volume":"41","author":"Haaland","year":"1997","journal-title":"Pediatric Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.cell.2010.07.032","article-title":"Fyn-tau-amyloid: a toxic triad","volume":"142","author":"Haass","year":"2010","journal-title":"Cell"},{"key":"B27","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":"Hagberg","year":"2015","journal-title":"Nat. Rev. Neurol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1146\/annurev.ne.17.030194.000335","article-title":"Cloned glutamate receptors","volume":"17","author":"Hollmann","year":"1994","journal-title":"Ann. Rev. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLEs risk of bias tool for animal studies","volume":"14","author":"Hooijmans","year":"2014","journal-title":"BMC Med. Res. Methodol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.brainres.2007.02.079","article-title":"Mechanism of Ca(2+)\/calmodulin-dependent protein kinase IV activation and of cyclic AMP response element binding protein phosphorylation during hypoxia in the cerebral cortex of newborn piglets","volume":"1150","author":"Hornick","year":"2007","journal-title":"Brain Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2014.10.040","article-title":"Dual role of Src kinase in governing neuronal survival","volume":"1594","author":"Hossain","year":"2015","journal-title":"Brain Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1111\/j.1440-1681.2011.05621.x","article-title":"Aberrant regulation and function of Src family tyrosine kinases: Their potential contributions to glutamate-induced neurotoxicity","volume":"39","author":"Hossain","year":"2012","journal-title":"Clin. Exper. Pharmacol. Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1471-2202-10-74","article-title":"Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia","volume":"10","author":"Hu","year":"2009","journal-title":"BMC Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.cell.2010.06.036","article-title":"Dendritic function of tau mediates amyloid-\u03b2 toxicity in alzheimers disease mouse models","volume":"142","author":"Ittner","year":"2010","journal-title":"Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"CD003311","DOI":"10.1002\/14651858.CD003311.pub3","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","volume":"1","author":"Jacobs","year":"2013","journal-title":"Cochr. Datab. System. Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1002\/ana.21365","article-title":"Activated Src kinases interact with the N -methyl-D-aspartate receptor after neonatal brain ischemia","volume":"63","author":"Jiang","year":"2008","journal-title":"Ann. Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0404.1991.tb04893.x","article-title":"Enhancement of GABA neurotransmission after cerebral ischemia in the rat reduces loss of hippocampal CA1 pyramidal cells","volume":"84","author":"Johansen","year":"1991","journal-title":"Acta Neurol. Scand."},{"key":"B38","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.clp.2013.09.004","article-title":"Pharmacologic neuroprotective strategies in neonatal brain injury","volume":"41","author":"Juul","year":"2014","journal-title":"Clin. Perinatol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/S0166-2236(96)01033-8","article-title":"The postsynaptic density at glutamatergic synapses","volume":"20","author":"Kennedy","year":"1997","journal-title":"Trends Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"16664","DOI":"10.1038\/s41598-017-16983-1","article-title":"Effect of Src Kinase inhibition on Cytochrome c, Smac\/DIABLO and apoptosis inducing factor (AIF) following cerebral hypoxia-ischemia in newborn piglets","volume":"7","author":"Kratimenos","year":"2017","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1159\/000480067","article-title":"Effect of concurrent src kinase inhibition with short-duration hypothermia on Ca2+\/calmodulin kinase IV activity and neuropathology after hypoxia-ischemia in the newborn swine brain","volume":"113","author":"Kratimenos","year":"2018","journal-title":"Neonatology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s11689-022-09431-3","article-title":"Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury","volume":"14","author":"Kratimenos","year":"2022","journal-title":"J. Neurodevelop. Diso"},{"key":"B43","doi-asserted-by":"publisher","first-page":"777","DOI":"10.3109\/00207454.2013.879869","article-title":"Pharmacological investigations on possible role of Src kinases in neuroprotective mechanism of ischemic postconditioning in mice","volume":"124","author":"Kumar","year":"2014","journal-title":"Int. J. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1007\/978-3-0348-8391-7_5","article-title":"Regulation of NMDA receptors by ethanol","volume":"54","author":"Kumari","year":"2000","journal-title":"Progr. Drug Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/S0140-6736(05)71048-5","article-title":"4 million neonatal deaths: when? Where? Why?","volume":"365","author":"Lawn","year":"2005","journal-title":"Lancet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"15366","DOI":"10.1074\/jbc.273.25.15366","article-title":"Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor","volume":"273","author":"Lee","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-3-7091-0693-8_13","article-title":"The dual role of SRC kinases in intracerebral hemorrhage","volume":"111","author":"Liu","year":"2011","journal-title":"Acta Neurochirurgica."},{"key":"B48","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.neulet.2004.12.054","article-title":"Suppression of Pyk2 attenuated the increased tyrosine phosphorylation of NMDA receptor subunit 2A after brain ischemia in rat hippocampus","volume":"379","author":"Liu","year":"2005","journal-title":"Neurosci. Lett."},{"key":"B49","doi-asserted-by":"publisher","first-page":"320","DOI":"10.3389\/fnins.2015.00320","article-title":"Mitochondria-controlled signaling mechanisms of brain protection in hypoxia","volume":"9","author":"Lukyanova","year":"2015","journal-title":"Front. Neurosci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1523\/JNEUROSCI.19-06-01988.1999","article-title":"Modification of postsynaptic densities after transient cerebral ischemia: a quantitative and three-dimensional ultrastructural study","volume":"19","author":"Martone","year":"1999","journal-title":"J. Neurosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.neulet.2009.05.041","article-title":"NO-mediated activation of Src kinase during hypoxia in the cerebral cortex of newborn piglets","volume":"460","author":"Mishra","year":"2009","journal-title":"Neurosci. Lett."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1007\/s11064-006-9204-x","article-title":"Nuclear Ca++-influx, Ca++\/calmodulin-dependent protein kinase IV activity and CREB protein phosphorylation during post-hypoxic reoxygenation in neuronal nuclei of newborn piglets: The role of nitric oxide","volume":"31","author":"Mishra","year":"2006","journal-title":"Neurochem. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.siny.2014.10.004","article-title":"Cooling in a low-resource environment: Lost in translation","volume":"20","author":"Montaldo","year":"2015","journal-title":"Semin. Fetal Neonatal Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1651-2227.1989.tb11276.x","article-title":"Cerebral blood flow during experimental hypoxaemia and ischaemia in the newborn piglet","volume":"360","author":"Odden","year":"1989","journal-title":"Acta Paediatr. Scand."},{"key":"B56","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1007\/BF00968557","article-title":"Modification of chloride flux across brain membranes by inhibitory amino acids in developing and adult mice","volume":"15","author":"Oja","year":"1990","journal-title":"Neurochem. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e591","DOI":"10.1542\/peds.2012-0891","article-title":"Optimizing therapeutic hypothermia for neonatal encephalopathy","volume":"131","author":"Olsen","year":"2013","journal-title":"Pediatrics"},{"key":"B58","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/84675","article-title":"Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke","volume":"7","author":"Paul","year":"2001","journal-title":"Nat. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e58834","DOI":"10.1371\/journal.pone.0058834","article-title":"Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis","volume":"8","author":"Pauliah","year":"2013","journal-title":"PLoS ONE"},{"key":"B60","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3389\/fneur.2013.00036","article-title":"Comparison of brain maturation among species: an example in translational research suggesting the possible use of bumetanide in newborn","volume":"4","author":"Pressler","year":"2013","journal-title":"Front. Neurol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1139\/Y08-100","article-title":"Diethyl dithiocarbamic acid, a possible nuclear factor kappa B inhibitor, attenuates ischemic postconditioning-induced attenuation of cerebral ischemia\u2013reperfusion injury in mice","volume":"87","author":"Rehni","year":"2009","journal-title":"Canad. J. Physiol. Pharmacol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1111\/j.1472-8206.2008.00567.x","article-title":"Implication of mast cell degranulation in ischemic preconditioning-induced prevention of cerebral injury","volume":"22","author":"Rehni","year":"","journal-title":"Fundam. Clin. Pharmacol."},{"key":"B63","first-page":"904","article-title":"Pharmacological preconditioning of the brain: a possible interplay between opioid and calcitonin gene related peptide transduction systems","volume":"60","author":"Rehni","year":"","journal-title":"Pharmacol. Rep."},{"key":"B64","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.lfs.2011.02.024","article-title":"Involvement of src-kinase activation in ischemic preconditioning induced protection of mouse brain","volume":"88","author":"Rehni","year":"2011","journal-title":"Life Sci"},{"key":"B65","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/S0140-6736(08)61329-X","article-title":"Therapeutic hypothermia for birth asphyxia in low-resource settings: a pilot randomised controlled trial","volume":"372","author":"Robertson","year":"2008","journal-title":"Lancet"},{"key":"B66","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1161\/01.STR.21.1.138","article-title":"Baclofen does not protect against cerebral ischemia in rats","volume":"21","author":"Rosenbaum","year":"1990","journal-title":"Stroke"},{"key":"B67","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nrn1368","article-title":"Src kinases: a hub for NMDA receptor regulation","volume":"5","author":"Salter","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/S0140-6736(79)91556-3","article-title":"Cell number and cell size: organ growth and development and the control of catch-up growth in rats","volume":"2","author":"Sands","year":"1979","journal-title":"Lancet."},{"key":"B69","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/0166-2236(93)90093-2","article-title":"The TINS\/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels","volume":"16","author":"Seeburg","year":"1993","journal-title":"Trends Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1056\/NEJMoa1112066","article-title":"Childhood outcomes after hypothermia for neonatal encephalopathy","volume":"366","author":"Shankaran","year":"2012","journal-title":"New Engl. J. Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0301-0082(91)90036-Z","article-title":"GABA receptor mechanisms in the central nervous system","volume":"36","author":"Sivilotti","year":"1991","journal-title":"Progr. Neurobiol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/jnr.1052","article-title":"Attenuation of malonate toxicity in primary mesencephalic cultures using the GABA transport blocker, NO-711","volume":"64","author":"Stokes","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1006\/abbi.1999.1374","article-title":"Rapid and Irreversible Inactivation of Protein Tyrosine Phosphatases PTP1B, CD45, and LAR by Peroxynitrite","volume":"369","author":"Takakura","year":"1999","journal-title":"Arch. Biochem. Biophys."},{"key":"B74","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jpeds.2011.12.047","article-title":"Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy","volume":"161","author":"Tam","year":"2012","journal-title":"J. Pediatr."},{"key":"B75","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1203\/00006450-199611000-00014","article-title":"A piglet survival model of posthypoxic encephalopathy","volume":"40","author":"Thoresen","year":"1996","journal-title":"Pediatr. Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/1471-2202-10-139","article-title":"Non-receptor tyrosine kinase Src is required for ischemia-stimulated neuronal cell proliferation via Raf\/ERK\/CREB activation in the dentate gyrus","volume":"10","author":"Tian","year":"2009","journal-title":"BMC Neurosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1093\/ilar.44.2.85","article-title":"Animal models of focal and global cerebral ischemia","volume":"44","author":"Traystman","year":"2003","journal-title":"ILAR J."},{"key":"B78","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1053\/j.semperi.2015.12.003","article-title":"Drugs for neuroprotection after birth asphyxia: Pharmacologic adjuncts to hypothermia","volume":"40","author":"Van Bel","year":"2016","journal-title":"Semin. Perinatol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.neulet.2003.11.061","article-title":"Activation of ERK5 is mediated by N-methyl-D-aspartate receptor and L-type voltage-gated calcium channel via Src involving oxidative stress after cerebral ischemia in rat hippocampus","volume":"357","author":"Wang","year":"2004","journal-title":"Neurosci. Lett."},{"key":"B80","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.neuroscience.2008.08.006","article-title":"Dual inhibitory roles of geldanamycin on the c-Jun NH2-terminal kinase 3 signal pathway through suppressing the expression of mixed-lineage kinase 3 and attenuating the activation of apoptosis signal-regulating kinase 1 via facilitating the activation of","volume":"156","author":"Wen","year":"2008","journal-title":"Neuroscience."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0022-510X(00)00386-5","article-title":"Brain ischemia and reperfusion: molecular mechanisms of neuronal injury","volume":"179","author":"White","year":"2000","journal-title":"J. Neurol. Sci"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.3174\/ajnr.A3423","article-title":"Brain injury patterns in hypoglycemia in neonatal encephalopathy","volume":"34","author":"Wong","year":"2013","journal-title":"Am. J. Neuroradiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1080\/02699050801911295","article-title":"Spry2-mediated inhibition of the Ras\/ERK pathway through interaction with Src kinase following cerebral ischemia","volume":"22","author":"Wu","year":"2008","journal-title":"Brain Injury"},{"key":"B84","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1542\/peds.2006-2839","article-title":"Determinants of outcomes after head cooling for neonatal encephalopathy","volume":"119","author":"Wyatt","year":"2007","journal-title":"Pediatrics"},{"key":"B85","doi-asserted-by":"publisher","first-page":"29355","DOI":"10.1074\/jbc.M800393200","article-title":"Neuroprotection of GluR5-containing kainate receptor activation against ischemic brain injury through decreasing tyrosine phosphorylation of N-methyl-D-aspartate receptors mediated by Src kinase","volume":"283","author":"Xu","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.neuroscience.2007.09.070","article-title":"Activation of GABA receptors attenuates neuronal apoptosis through inhibiting the tyrosine phosphorylation of NR2A by Src after cerebral ischemia and reperfusion","volume":"150","author":"Zhang","year":"2007","journal-title":"Neuroscience."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.1049655\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T11:44:08Z","timestamp":1669290248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.1049655\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":86,"alternative-id":["10.3389\/fnins.2022.1049655"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.1049655","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]},"article-number":"1049655"}}