{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:28:30Z","timestamp":1776079710877,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Birth asphyxia causes brain injury in neonates, but a fully successful treatment has yet to be developed. This study aimed to investigate the effect of group II mGlu receptors activation after experimental birth asphyxia (hypoxia-ischemia) on the expression of factors involved in apoptosis and neuroprotective neurotrophins. Hypoxia-ischemia (HI) on 7-day-old rats was used as an experimental model. The effects of intraperitoneal application of mGluR2 agonist LY379268 (5\u2009mg\/kg) and the specific mGluR3 agonist NAAG (5\u2009mg\/kg) (1 h or 6 h after HI) on apoptotic processes and initiation of the neuroprotective mechanism were investigated. LY379268 and NAAG applied shortly after HI prevented brain damage and significantly decreased pro-apoptotic Bax and HtrA2\/Omi expression, increasing expression of anti-apoptotic Bcl-2. NAAG or LY379268 applied at both times also decreased HIF-1\u03b1 formation. HI caused a significant decrease in BDNF concentration, which was restored after LY379268 or NAAG administration. HI-induced increase in GDNF concentration was decreased after administration of LY379268 or NAAG. Our results show that activation of mGluR2\/3 receptors shortly after HI prevents brain damage by the inhibition of excessive glutamate release and apoptotic damage decrease. mGluR2 and mGluR3 agonists produced comparable results, indicating that both receptors may be a potential target for early treatment in neonatal HI.<\/jats:p>","DOI":"10.3390\/ijms23137000","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T21:25:00Z","timestamp":1656019500000},"page":"7000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Group II Metabotropic Glutamate Receptors Reduce Apoptosis and Regulate BDNF and GDNF Levels in Hypoxic-Ischemic Injury in Neonatal Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1840-0267","authenticated-orcid":false,"given":"Ewelina","family":"Bratek-Gerej","sequence":"first","affiliation":[{"name":"Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apolonia","family":"Ziembowicz","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4212-221X","authenticated-orcid":false,"given":"Elzbieta","family":"Salinska","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.earlhumdev.2010.05.010","article-title":"Epidemiology of neonatal encephalopathy and hypoxic\u2013ischaemic encephalopathy","volume":"86","author":"Kurinczuk","year":"2010","journal-title":"Early Hum. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fneur.2015.00198","article-title":"Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy\u2014Where to from Here?","volume":"6","author":"Davidson","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S1474-4422(08)70294-1","article-title":"Brain injury in premature infants: A complex amalgam of destructive and developmental disturbances","volume":"8","author":"Volpe","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_4","first-page":"800","article-title":"Neuroprotective effects of LY379268, a selective mGlu2\/3 receptor agonist: Investigations into possible mechanism of action in vivo","volume":"294","author":"Bond","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1097\/00001756-199804200-00006","article-title":"The mGlu receptor ligand (S)-4C3HPG protects neurons after global ischaemia in gerbils","volume":"9","author":"Hatton","year":"1998","journal-title":"Neuroreport"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.1523\/JNEUROSCI.23-14-06023.2003","article-title":"Group II Metabotropic Glutamate Receptors Regulate the Vulnerability to Hypoxic Brain Damage","volume":"23","author":"Poli","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bratek, E., Ziembowicz, A., Bronisz, A., and Salinska, E. (2018). The activation of group II metabotropic glutamate receptors protects neonatal rat brains from oxidative stress injury after hypoxia-ischemia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200933"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8848015","DOI":"10.1155\/2021\/8848015","article-title":"Pretreatment with mGluR2 or mGluR3 Agonists Reduces Apoptosis Induced by Hypoxia-Ischemia in Neonatal Rat Brains","volume":"2021","author":"Bronisz","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108799","DOI":"10.1016\/j.neuropharm.2021.108799","article-title":"Membrane trafficking and positioning of mGluRs at presynaptic and postsynaptic sites of excitatory synapses","volume":"200","author":"Bodzeta","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuroscience.2014.12.083","article-title":"Developmental decline in modulation of glutamatergic synapses in layer IV of the barrel cortex by group II metabotropic glutamate receptors","volume":"290","author":"Mateo","year":"2015","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.4236\/jbise.2014.713100","article-title":"Differential expression of mGluR2 in the developing cerebral cortex of the mouse","volume":"7","author":"Venkatadri","year":"2014","journal-title":"J. Biomed. Sci. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1006\/nbdi.2000.0371","article-title":"Early Neurodegeneration after Hypoxia-Ischemia in Neonatal Rat Is Necrosis while Delayed Neuronal Death Is Apoptosis","volume":"8","author":"Northington","year":"2001","journal-title":"Neurobiol. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ana.22419","article-title":"Neuronal cell death in neonatal hypoxia-ischemia","volume":"69","author":"Northington","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1006\/nbdi.1999.0275","article-title":"BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia","volume":"7","author":"Han","year":"2000","journal-title":"Neurobiol. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhu, P., Fujino, M., Zhuang, J., Guo, H., Sheikh, I., Zhao, L., and Li, X.-K. (2016). Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122078"},{"key":"ref_16","first-page":"1194","article-title":"Adenovirus-mediated bcl-2 gene transfer inhibits renal ischemia\/reperfusion induced tubular oxidative stress and apoptosis","volume":"5","author":"Chien","year":"2005","journal-title":"Am. J. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0092-8674(00)80434-1","article-title":"Cytochrome c and dATP-dependent formation of Apaf-1\/caspase-9 complex initiates an apoptotic protease cascade","volume":"91","author":"Li","year":"1997","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1177\/0883073809338212","article-title":"Apoptotic mechanisms in the immature brain: Involvement of mitochondria","volume":"24","author":"Hagberg","year":"2009","journal-title":"J. Child Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1755-5922.2008.00052.x","article-title":"Activation of HtrA2, a mitochondrial serine protease mediates apoptosis: Current knowledge on HtrA2 mediated myocardial ischemia\/reperfusion injury","volume":"26","author":"Bhuiyan","year":"2008","journal-title":"Cardiovasc. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1515\/revneuro-2018-0004","article-title":"Progress in research on the role of Omi\/HtrA2 in neurological diseases","volume":"30","author":"Su","year":"2019","journal-title":"Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.nbd.2004.01.014","article-title":"X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia\u2013ischemia","volume":"16","author":"Wang","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.expneurol.2008.10.016","article-title":"Prodeath or prosurvival: Two facets of hypoxia inducible factor-1 in perinatal brain injury","volume":"216","author":"Chen","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1128\/MCB.24.7.2875-2889.2004","article-title":"Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance","volume":"24","author":"Erler","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_24","first-page":"905","article-title":"The role of TNF-\u03b1, IL-6, IL-10, and GDNF in neuronal apoptosis in neonatal rat with hypoxic-ischemic encephalopathy","volume":"18","author":"Li","year":"2014","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3892\/ijmm.2020.4625","article-title":"Silencing of long noncoding antisense RNA brainderived neurotrophic factor attenuates hypoxia\/ischemiainduced neonatal brain injury","volume":"46","author":"Qiao","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_26","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":"Xiong","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/j.1582-4934.2008.00671.x","article-title":"Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts","volume":"14","author":"Yasuhara","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9594","DOI":"10.1523\/JNEUROSCI.18-23-09594.1998","article-title":"Neuroprotection by glial metabotropic glutamate receptors is mediated by transforming growth factor-\u03b2","volume":"18","author":"Bruno","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.neuroscience.2009.11.012","article-title":"Group II metabotropic glutamate receptor activation by agonist LY379268 treatment increases the expression of brain derived neurotrophic factor in the mouse brain","volume":"165","author":"Bonomo","year":"2010","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1046\/j.1471-4159.2001.00056.x","article-title":"Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain-derived neurotrophic factor induction","volume":"76","author":"Matarredona","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Battaglia, G., Molinaro, G., Riozzi, B., Storto, M., Busceti, C.L., Spinsanti, P., Bucci, D., Di Liberto, V., Mud\u00f2, G., and Corti, C. (2009). Activation of mGlu3 receptors stimulates the production of GDNF in striatal neurons. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006591"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3892\/br.2012.48","article-title":"The neuroprotective roles of BDNF in hypoxic ischemic brain injury","volume":"1","author":"Chen","year":"2013","journal-title":"Biomed. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.brainresbull.2012.05.001","article-title":"Ultrasound-induced release of GDNF from lipid coated microbubbles injected into striatum reduces hypoxic-ischemic injury in neonatal rats","volume":"88","author":"Wang","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bratek, E., Ziembowicz, A., and Salinska, E. (2018). Pretreatment with Group II Metabotropic Glutamate Receptor Agonist LY379268 Protects Neonatal Rat Brains from Oxidative Stress in an Experimental Model of Birth Asphyxia. Brain Sci., 8.","DOI":"10.3390\/brainsci8030048"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bratek, E., Ziembowicz, A., and Salinska, E. (2020). N-Acetylaspartylglutamate (NAAG) Pretreatment Reduces Hypoxic-Ischemic Brain Damage and Oxidative Stress in Neonatal Rats. Antioxidants, 9.","DOI":"10.3390\/antiox9090877"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.5409\/wjcp.v5.i1.67","article-title":"Short and long term prognosis in perinatal asphyxia: An update","volume":"5","author":"Ahearne","year":"2016","journal-title":"World J. Clin. Pediatr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1891\/0730-0832.37.3.155","article-title":"The Six-Hour Window: How the Community Hospital Nursery Can Optimize Outcomes of the Infant with Suspected Hypoxic-Ischemic Encephalopathy","volume":"37","author":"Ibrani","year":"2018","journal-title":"Neonatal Netw."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.jped.2015.07.004","article-title":"Hypothermia therapy for newborns with hypoxic ischemic encephalopathy","volume":"91","author":"Silveira","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0146-0005(03)00047-8","article-title":"Challenge of conducting trials of neuroprotection in the asphyxiated term infant","volume":"27","author":"Shankaran","year":"2003","journal-title":"Semin. Perinatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0014-2999(02)01289-X","article-title":"Neuroprotective effects of N-acetylaspartylglutamate in a neonatal rat model of hypoxia-ischemia","volume":"437","author":"Cai","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00213-007-0974-x","article-title":"The mGlu2 but not the mGlu3 receptor mediates the actions of the mGluR2\/3 agonist, LY379268, in mouse models predictive of antipsychotic activity","volume":"196","author":"Woolley","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/syn.20553","article-title":"Altered hippocampal expression of glutamate receptors and transporters in GRM2 and GRM3 knockout mice","volume":"62","author":"Lyon","year":"2008","journal-title":"Synapse"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/j.1471-4159.2011.07380.x","article-title":"N-acetylaspartylglutamate is an agonist at mGluR(3) in vivo and in vitro","volume":"119","author":"Neale","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e145","DOI":"10.1038\/tp.2012.68","article-title":"NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia","volume":"2","author":"Olszewski","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1007\/s11064-008-9649-1","article-title":"Hypoxia ischemia-mediated cell death in neonatal rat brain","volume":"33","author":"Gill","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6320","DOI":"10.1523\/JNEUROSCI.0449-07.2007","article-title":"Neuron-specific inactivation of the hypoxia inducible factor 1 \u03b1 increases brain injury in a mouse model of transient focal cerebral ischemia","volume":"27","author":"Baranova","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14871","DOI":"10.1074\/jbc.M400461200","article-title":"Prolonged hypoxia differentially regulates hypoxia-inducible factor (HIF)-1\u03b1 and HIF-2\u03b1 expression in lung epithelial cells: Implication of natural antisense HIF-1\u03b1","volume":"279","author":"Uchida","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1523\/JNEUROSCI.4555-04.2005","article-title":"Brain-specific knock-out of hypoxia-inducible factor-1\u03b1 reduces rather than increases hypoxic-ischemic damage","volume":"25","author":"Helton","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11024","DOI":"10.1073\/pnas.191352298","article-title":"Calcium regulation of neuronal gene expression","volume":"98","author":"West","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3109\/08977194.2012.691478","article-title":"Neuroprotection by GDNF in the ischemic brain","volume":"30","author":"Duarte","year":"2012","journal-title":"Growth Factors"},{"key":"ref_52","first-page":"3006","article-title":"BDNF diminishes caspase-2 but not c-Jun immunoreactivity of neurons in retinal ganglion cell layer after transient ischemia","volume":"40","author":"Kurokawa","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3109\/10611860903318134","article-title":"Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS","volume":"18","author":"Lee","year":"2010","journal-title":"J. Drug Target."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.nbd.2012.03.025","article-title":"The group 2 metabotropic glutamate receptor agonist LY379268 rescues neuronal, neurochemical and motor abnormalities in R6\/2 Huntington\u2019s disease mice","volume":"47","author":"Reiner","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.brainres.2012.07.026","article-title":"BDNF may play a differential role in the protective effect of the mGluR2\/3 agonist LY379268 on striatal projection neurons in R6\/2 Huntington\u2019s disease mice","volume":"1473","author":"Reiner","year":"2012","journal-title":"Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.neuropharm.2011.05.006","article-title":"mGluR2\/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Erk1\/2 in mouse striatum","volume":"61","author":"Mudo","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0736-5748(99)00057-X","article-title":"Expression of glial cell line-derived neurotrophic factor in the brain and cerebrospinal fluid of the developing rat","volume":"17","author":"Ikeda","year":"1999","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0736-5748(01)00042-9","article-title":"Expression of glial cell line-derived neurotrophic factor (GDNF) in the developing human fetal brain","volume":"19","author":"Koo","year":"2001","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0736-5748(02)00082-5","article-title":"Bimodal upregulation of glial cell line-derived neurotrophic factor (GDNF) in the neonatal rat brain following ischemic\/hypoxic injury","volume":"20","author":"Ikeda","year":"2002","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zalewska, T., Jaworska, J., Sypecka, J., and Ziemka-Nalecz, M. (2020). Impact of a Histone Deacetylase Inhibitor-Trichostatin A on Neurogenesis after Hypoxia-Ischemia in Immature Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113808"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/dev.22011","article-title":"Expression of synaptophysin and BDNF in the medial prefrontal cortex following early life stress and neonatal hypoxia-ischemia","volume":"63","author":"Tata","year":"2021","journal-title":"Dev. Psychobiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ahn, S.Y., Sung, D.K., Chang, Y.S., Sung, S.I., Kim, Y.E., Kim, H.J., Lee, S.M., and Park, W.S. (2021). BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111395"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1159\/000489808","article-title":"Neuroprotection Against Hypoxic\/Ischemic Injury: Delta-Opioid Receptors and BDNF-TrkB Pathway","volume":"47","author":"Sheng","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.1097\/00001756-199912160-00037","article-title":"Protection of neonatal rat brain from hypoxic-ischemic injury by LY379268, a Group II metabotropic glutamate receptor agonist","volume":"10","author":"Cai","year":"1999","journal-title":"Neuroreport"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7000\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:38:55Z","timestamp":1760139535000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":64,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137000"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137000","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,23]]}}}