{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:26:17Z","timestamp":1787984777528,"version":"build-2784847793"},"reference-count":70,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BONFOR SciMed-Stipendium","award":["2021-4-29"],"award-info":[{"award-number":["2021-4-29"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Hypoxic-ischemic encephalopathy (HIE) is a common type of brain injury caused by a lack of oxygen and blood flow to the brain during the perinatal period. The incidence of HIE is approximately 2\u20133 cases per 1000 live births in high-income settings; while in low- and middle-income countries, the incidence is 3\u201310-fold higher. Therapeutic hypothermia (TH) is the current standard treatment for neonates affected by moderate\u2013severe HIE. However, more than 50% of all infants with suspected HIE have mild encephalopathy, and these infants are not treated with TH because of their lower risk of adverse outcomes. Despite this, several analyses of pooled data provide increasing evidence that infants who initially have mild encephalopathy may present signs of more significant brain injury later in life. The purpose of this study was to expand our knowledge about the effect of mild\u2013moderate hypoxia-ischemia (HI) at the cellular, structural, and functional levels. An established rat model of mild\u2013moderate HI was used, where postnatal day (P) 7 rats were exposed to unilateral permanent occlusion of the left carotid artery and 90 min of 8% hypoxia, followed by TH or normothermia (NT) treatment. The extent of injury was assessed using histology (P14 and P42) and MRI (P11 and P32), as well as with short-term and long-term behavioral tests. Neurogenesis was assessed by BrdU staining. We showed that mild\u2013moderate HI leads to a progressive loss of brain tissue, pathological changes in MRI scans, as well as an impairment of long-term motor function. At P14, the median area loss assessed by histology for HI animals was 20% (p &lt; 0.05), corresponding to mild\u2013moderate brain injury, increasing to 55% (p &lt; 0.05) at P42. The data assessed by MRI corroborated our results. HI led to a decrease in neurogenesis, especially in the hippocampus and the lateral ventricle at early time points, with a delayed partial recovery. TH was not neuroprotective at early time points following mild\u2013moderate HI, but prevented the increase in brain damage over time. Additionally, rats treated with TH showed better long-term motor function. Altogether, our results bring more light to the understanding of pathophysiology following mild-moderate HI. We showed that, in the context of mild-moderate HI, TH failed to be significantly neuroprotective. However, animals treated with TH showed a significant improvement in motor, but not cognitive long-term function. These results are in line with what is observed in some cases where neonates with mild HIE are at risk of neurodevelopmental deficits in infancy or childhood. Whether TH should be used as a preventive treatment to reduce adverse outcomes in mild-HIE remains of active interest, and more research has to be carried out in order to address this question.<\/jats:p>","DOI":"10.3390\/life12081164","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T02:06:42Z","timestamp":1659319602000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Impact of Hypoxia-Ischemia on Neurogenesis and Structural and Functional Outcomes in a Mild\u2013Moderate Neonatal Hypoxia-Ischemia Brain Injury Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Anne","family":"Ehlting","sequence":"first","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care, Children\u2019s Hospital, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Zweyer","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care, Children\u2019s Hospital, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Maes","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care, Children\u2019s Hospital, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Schleehuber","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care, Children\u2019s Hospital, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik","family":"Doshi","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemmen","family":"Sabir","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care, Children\u2019s Hospital, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Bernis","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care, Children\u2019s Hospital, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1080\/14737175.2017.1259567","article-title":"Neonatal hypoxic ischemic encephalopathy: An update on disease pathogenesis and treatment","volume":"17","author":"Yildiz","year":"2017","journal-title":"Expert. Rev. Neurother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11910-019-0916-0","article-title":"Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy","volume":"19","author":"Wassink","year":"2019","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1080\/14767058.2018.1468881","article-title":"Neonatal hypoxic\u2013ischemic encephalopathy: Emerging therapeutic strategies based on pathophysiologic phases of the injury","volume":"32","author":"Wang","year":"2018","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s13760-020-01308-3","article-title":"Pathophysiology of hypoxic\u2013ischemic encephalopathy: A review of the past and a view on the future","volume":"120","author":"Greco","year":"2020","journal-title":"Acta Neurol. Belg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105541","DOI":"10.1016\/j.earlhumdev.2022.105541","article-title":"Long-term neuropsychological and behavioral outcome of mild and moderate hypoxic ischemic encephalopathy","volume":"165","author":"Halpin","year":"2022","journal-title":"Early Hum. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, Y., Wisnowski, J.L., Chalak, L., Mathur, A.M., McKinstry, R.C., Licona, G., Mayock, D.E., Chang, T., Van Meurs, K.P., and Wu, T.-W. (2022). Mild hypoxic-ischemic encephalopathy (HIE): Timing and pattern of MRI brain injury. Pediatr. Res.","DOI":"10.1038\/s41390-022-02026-7"},{"key":"ref_7","first-page":"4901014","article-title":"Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury","volume":"2016","author":"Hristova","year":"2016","journal-title":"Neural Plast."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101257","DOI":"10.1016\/j.siny.2021.101257","article-title":"Unanswered questions regarding therapeutic hypothermia for neonates with neonatal encephalopathy","volume":"26","author":"Sabir","year":"2021","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_9","first-page":"CD003311","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","volume":"2013","author":"Jacobs","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.resuscitation.2013.12.006","article-title":"Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic\u2013ischemic brain injury","volume":"85","author":"Osredkar","year":"2014","journal-title":"Resuscitation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1161\/STROKEAHA.112.674481","article-title":"Immediate Hypothermia Is Not Neuroprotective After Severe Hypoxia-Ischemia and Is Deleterious When Delayed by 12 Hours in Neonatal Rats","volume":"43","author":"Sabir","year":"2012","journal-title":"Stroke"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1136\/archdischild-2018-315711","article-title":"Therapeutic hypothermia for mild neonatal encephalopathy: A systematic review and meta-analysis","volume":"105","author":"Kariholu","year":"2018","journal-title":"Arch. Dis. Child.-Fetal Neonatal Ed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/jcbfm.2013.3","article-title":"The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment","volume":"33","author":"Donega","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_14","first-page":"396","article-title":"Neurogenesis in the embryonic and adult brain: Same regulators, different roles","volume":"8","author":"Guillemot","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00441-017-2658-0","article-title":"Home sweet home: The neural stem cell niche throughout development and after injury","volume":"371","author":"Ruddy","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12974-020-1706-y","article-title":"Neonatal hypoxia-ischemia in rat elicits a region-specific neurotrophic response in SVZ microglia","volume":"17","author":"Fisch","year":"2020","journal-title":"J. Neuroinflam."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1002\/glia.22858","article-title":"Effects of Microglia on Neurogenesis","volume":"63","author":"Sato","year":"2015","journal-title":"Glia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1111\/ejn.13612","article-title":"Neonatal hypoxia-ischemia in rat increases doublecortin concentration in the cerebrospinal fluid","volume":"46","author":"Fisch","year":"2017","journal-title":"Eur. J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1159\/000430862","article-title":"Effects of Neonatal Hypoxic-Ischemic Injury and Hypothermic Neuroprotection on Neural Progenitor Cells in the Mouse Hippocampus","volume":"37","author":"Kwak","year":"2015","journal-title":"Dev. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000046149","article-title":"Hypoxia\/Ischemia Depletes the Rat Perinatal Subventricular Zone of Oligodendrocyte Progenitors and Neural Stem Cells","volume":"23","author":"Levison","year":"2001","journal-title":"Dev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/nprot.2006.224","article-title":"BrdU assay for neurogenesis in rodents","volume":"1","author":"Wojtowicz","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2479626","DOI":"10.1155\/2022\/2479626","article-title":"Temporal Characterization of Microglia-Associated Pro- and Anti-Inflammatory Genes in a Neonatal Inflammation-Sensitized Hypoxic-Ischemic Brain Injury Model","volume":"2022","author":"Bernis","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"540878","DOI":"10.3389\/fneur.2020.540878","article-title":"Involvement of CXCL1\/CXCR2 During Microglia Activation Following Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats","volume":"11","author":"Serdar","year":"2020","journal-title":"Front. Neurol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3389\/fncel.2019.00237","article-title":"Early Pro-inflammatory Microglia Activation After Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats","volume":"13","author":"Serdar","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1159\/000455838","article-title":"Hypothermic Neuronal Rescue from Infection-Sensitised Hypoxic-Ischaemic Brain Injury Is Pathogen Dependent","volume":"39","author":"Falck","year":"2017","journal-title":"Dev. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1159\/000487798","article-title":"Hypothermia Is Neuroprotective after Severe Hypoxic-Ischaemic Brain Injury in Neonatal Rats Pre-Exposed to PAM3CSK4","volume":"40","author":"Falck","year":"2018","journal-title":"Dev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1159\/000430860","article-title":"Hypothermia Does Not Reverse Cellular Responses Caused by Lipopolysaccharide in Neonatal Hypoxic-Ischaemic Brain Injury","volume":"37","author":"Osredkar","year":"2015","journal-title":"Dev. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sabir, H., Wall\u00f8e, L., Dingley, J., Smit, E., Liu, X., and Thoresen, M. (2014). Combined treatment of xenon and hypothermia in newborn rats--additive or synergistic effect?. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109845"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23430","DOI":"10.1038\/srep23430","article-title":"Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia","volume":"6","author":"Wood","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10833","DOI":"10.1038\/s41598-020-67532-2","article-title":"Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic\u2013ischaemic brain injury: A single laboratory meta-analysis","volume":"10","author":"Wood","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3349\/ymj.2020.61.6.492","article-title":"Cellular Response of Ventricular-Subventricular Neural Progenitor\/Stem Cells to Neonatal Hypoxic-Ischemic Brain Injury and Their Enhanced Neurogenesis","volume":"61","author":"Shin","year":"2020","journal-title":"Yonsei Med. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6270700","DOI":"10.1155\/2022\/6270700","article-title":"Deep Learning-Based Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Ischemic Penumbra in Early Cerebral Infarction","volume":"2022","author":"Sheng","year":"2022","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Parmentier, C.E.J., de Vries, L.S., and Groenendaal, F. (2022). Magnetic Resonance Imaging in (Near-)Term Infants with Hypoxic-Ischemic Encephalopathy. Diagnostics, 12.","DOI":"10.3390\/diagnostics12030645"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.earlhumdev.2015.07.008","article-title":"Neonatal neurobehavior after therapeutic hypothermia for hypoxic ischemic encephalopathy","volume":"91","author":"Massaro","year":"2015","journal-title":"Early Hum. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"598788","DOI":"10.3389\/fendo.2021.598788","article-title":"Effects of Melatonin on Neurobehavior and Cognition in a Cerebral Palsy Model of plppr5-\/- Mice","volume":"12","author":"Sun","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s12974-019-1595-0","article-title":"Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat","volume":"16","author":"Borjini","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ch\u00e1vez-Guti\u00e9rrez, E., Fuentes-Venado, C.E., Rodr\u00edguez-P\u00e1ez, L., Guerra-Araiza, C., Larqu\u00e9, C., Mart\u00ednez-Herrera, E., Ocharan-Hern\u00e1ndez, M.E., Lomel\u00ed, J., Loza-Mej\u00eda, M.A., and Salazar, J.R. (2022). High Fructose and High Fat Diet Impair Different Types of Memory through Oxidative Stress in a Sex- and Hormone-Dependent Manner. Metabolites, 12.","DOI":"10.3390\/metabo12040341"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000502936","article-title":"Outcomes of Infants with Mild Hypoxic Ischemic Encephalopathy Who Did Not Receive Therapeutic Hypothermia","volume":"4","author":"Reiss","year":"2019","journal-title":"Biomed. Hub"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1177\/0883073819828625","article-title":"Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy","volume":"34","author":"Saw","year":"2019","journal-title":"J. Child. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1055\/s-0040-1716341","article-title":"Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children\u2019s Hospital Neonatal Consortium","volume":"39","author":"Rao","year":"2022","journal-title":"Am. J. Perinatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1055\/s-0038-1676973","article-title":"Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia","volume":"36","author":"Rao","year":"2019","journal-title":"Am. J. Perinatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/ana.23647","article-title":"Neonatal encephalopathy: An inadequate term for hypoxic-ischemic encephalopathy","volume":"72","author":"Volpe","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3345\/cep.2021.00164","article-title":"Cognitive outcomes in late childhood and adolescence of neonatal hypoxic-ischemic encephalopathy","volume":"64","author":"Lee","year":"2021","journal-title":"Clin. Exp. Pediatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1203\/00006450-199707000-00009","article-title":"Late Glial Swelling after Acute Cerebral Hypoxia-Ischemia in the Neonatal Rat: A Combined Magnetic Resonance and Histochemical Study","volume":"42","author":"Rumpel","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5985806","DOI":"10.1155\/2022\/5985806","article-title":"The Evaluation Value of Diffusion-Weighted Imaging for Brain Injury in Patients after Deep Hypothermic Circulatory Arrest","volume":"2022","author":"Zhuang","year":"2022","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1089\/neu.2005.22.857","article-title":"Diffusion-Weighted Imaging of Edema following Traumatic Brain Injury in Rats: Effects of Secondary Hypoxia","volume":"22","author":"Bouwhuis","year":"2005","journal-title":"J. Neurotrauma"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Alegiani, A.C., MacLean, S., Braass, H., Siemonsen, S., Gerloff, C., Fiehler, J., Cho, T.-H., Derex, L., Hermier, M., and Berthez\u00e8ne, Y. (2017). Comprehensive analysis of early fractional anisotropy changes in acute ischemic stroke. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188318"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/jon.12362","article-title":"Brain Connectivity and Functional Recovery in Patients With Ischemic Stroke","volume":"27","author":"Almeida","year":"2016","journal-title":"J. Neuroimaging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1080\/10717544.2022.2064562","article-title":"Pathogenic mechanisms and therapeutic promise of phytochemicals and nanocarriers based drug delivery against radiotherapy-induced neurotoxic manifestations","volume":"29","author":"Iqubal","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.brainres.2008.02.037","article-title":"Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke","volume":"1208","author":"Kadam","year":"2008","journal-title":"Brain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1203\/01.PDR.0000179381.86809.02","article-title":"Hypoxic-Ischemic Injury Stimulates Subventricular Zone Proliferation and Neurogenesis in the Neonatal Rat","volume":"58","author":"Ong","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1523\/JNEUROSCI.1898-05.2006","article-title":"Neural Stem\/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia\/Ischemia","volume":"26","author":"Felling","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.ajog.2005.01.029","article-title":"Limited differentiation to neurons and astroglia from neural stem cells in the cortex and striatum after ischemia\/hypoxia in the neonatal rat brain","volume":"193","author":"Ikeda","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/aps.2013.89","article-title":"Inflammatory responses in hypoxic ischemic encephalopathy","volume":"34","author":"Liu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1111\/j.1460-9568.2009.06870.x","article-title":"IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit of neuroblasts from the subventricular zone","volume":"30","author":"Bulfone","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.4103\/1673-5374.303033","article-title":"Brain-derived neurotrophic factor and its related enzymes and receptors play important roles after hypoxic-ischemic brain damage","volume":"16","author":"Yang","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_57","first-page":"52","article-title":"IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain","volume":"10","author":"Defterali","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.neuroimage.2015.10.084","article-title":"Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults","volume":"131","author":"Maass","year":"2016","journal-title":"Neuroimage"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fnins.2016.00026","article-title":"Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles","volume":"10","author":"Vilar","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Colucci-D\u2019Amato, L., Speranza, L., and Volpicelli, F. (2020). Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207777"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-2094-8-12","article-title":"Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice","volume":"8","author":"Park","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000454949","article-title":"Therapeutic Hypothermia Provides Variable Protection against Behavioral Deficits after Neonatal Hypoxia-Ischemia: A Potential Role for Brain-Derived Neurotrophic Factor","volume":"39","author":"Diaz","year":"2017","journal-title":"Dev. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ibneur.2022.04.008","article-title":"Early life stress influences basal ganglia dopamine receptors and novel object recognition of adolescent and adult rats","volume":"12","author":"Sinani","year":"2022","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"152327","DOI":"10.1016\/j.tox.2019.152327","article-title":"Gestational and perinatal exposure to diazinon causes long-lasting neurobehavioral consequences in the rat","volume":"429","author":"Hawkey","year":"2019","journal-title":"Toxicology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/pr.2015.100","article-title":"Therapeutic hypothermia and hypoxia\u2013ischemia in the term-equivalent neonatal rat: Characterization of a translational preclinical model","volume":"78","author":"Patel","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.braindev.2018.01.003","article-title":"EPO improved neurologic outcome in rat pups late after traumatic brain injury","volume":"40","author":"Schober","year":"2018","journal-title":"Brain Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41372-021-01026-5","article-title":"Does mild hypoxic ischemic encephalopathy adversely affect neurodevelopmental outcome?","volume":"41","author":"Berube","year":"2021","journal-title":"J. Perinatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e20160659","DOI":"10.1542\/peds.2016-0659","article-title":"Early EEG Grade and Outcome at 5 Years After Mild Neonatal Hypoxic Ischemic Encephalopathy","volume":"138","author":"Murray","year":"2016","journal-title":"Pediatrics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1001\/jamapediatrics.2017.3044","article-title":"Mild Neonatal Encephalopathy-How, When, and How Much to Treat?","volume":"172","author":"Lodygensky","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.jpeds.2011.08.004","article-title":"Hypothermia and other treatment options for neonatal encephalopathy: An executive summary of the Eunice Kennedy Shriver NICHD workshop","volume":"159","author":"Higgins","year":"2011","journal-title":"J. Pediatr."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/8\/1164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:59:58Z","timestamp":1760140798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/8\/1164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,30]]},"references-count":70,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["life12081164"],"URL":"https:\/\/doi.org\/10.3390\/life12081164","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,30]]}}}