Perinatal hypoxia is still one of the greatest threats to the newborn child, even in developed countries. However, there is a lack of works which summarize up-to-date information about that huge topic. Our review covers a broader spectrum of recent results from studies on mechanisms leading to hypoxia-induced injury. It also resumes possible primary causes and observed behavioral outcomes of perinatal hypoxia. In this review, we recognize two types of hypoxia, according to the localization of its primary cause: environmental and placental. Later we analyze possible pathways of prenatal hypoxia-induced injury including gene expression changes, glutaminergic excitatory damage (and a role of NMDA receptors in it), oxidative stress with ROS and RNS production, inflammation and apoptosis. Moreover, we focus on the impact of these pathophysiological changes on the structure and development of the brain, especially on its regions: corpus striatum and hippocampus. These brain changes of the offspring lead to impairments in their postnatal growth and sensorimotor development, and in their motor functions, activity, emotionality and learning ability in adulthood. Later we compare various animal models used to investigate the impact of prenatal and postnatal injury (hypoxic, ischemic or combinatory) on living organisms, and show their advantages and limitations.

Centre of Experimental Medicine Slovak Academy of Sciences Bratislava Slovak Republic

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ABHIJIT S, SUBRAMANYAM MVV, DEVI SA. Grape seed proanthocyanidin and swimming exercise protects against cognitive decline: a study on m1 acetylcholine receptors in aging male rat brain. Neurochem Res. 2017;42:3573–3586. doi: 10.1007/s11064-017-2406-6. PubMed DOI

AOSAKI T, MIURA M, SUZUKI T, NISHIMURA K, MASUDA M. Acetylcholine-dopamine balance hypothesis in the striatum: An update: Acetylcholine-dopamine balance hypothesis. Geriatr Gerontol Int. 2010;10:S148–S157. doi: 10.1111/j.1447-0594.2010.00588.x. PubMed DOI

BALDUINI W, De ANGELIS V, MAZZONI E, CIMINO M. Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats. Brain Res. 2000;859:318–325. doi: 10.1016/S0006-8993(00)01997-1. PubMed DOI

BROWN DI, WILLIS MS, BERTHIAUME JM. The Scientist’s guide to cardiac metabolism. Elsevier; 2016. Influence of ischemia-reperfusion injury on cardiac metabolism; pp. 155–167. DOI

BURD I, WELLING J, KANNAN G, JOHNSTON MV. Excitotoxicity as a common mechanism for fetal neuronal injury with hypoxia and intrauterine inflammation. Adv Pharmacol. 2016;76:85–101. doi: 10.1016/bs.apha.2016.02.003. PubMed DOI

BUWALDA B, NYAKAS C, VOSSELMAN HJ, LUITEN PGM. Effects of early postnatal anoxia on adult learning and emotion in rats. Behav Brain Res. 1995;67:85–90. doi: 10.1016/0166-4328(94)00108-R. PubMed DOI

CAMM EJ, GIBBS ME, HARDING R, MULDER T, REES SM. Prenatal hypoxia impairs memory function but does not result in overt structural alterations in the postnatal chick brain. Dev Brain Res. 2005;160:9–18. doi: 10.1016/j.devbrainres.2005.07.015. PubMed DOI

CLERICI C, UCHIDA T, PLANÈS C, MATTHAY MA. Cell and molecular response to stress. Elsevier; 2002. Regulation of gene expression by hypoxia in lung alveolar epithelial cells; pp. 13–26. DOI

COOPER JR, BLOOM FE, ROTH RH. The biochemical basis of neuropharmacology. Oxford, New York: Oxford University Press; 2003.

COQ J-O, DELCOUR M, MASSICOTTE VS, BAUD O, BARBE MF. Prenatal ischemia deteriorates white matter, brain organization, and function: implications for prematurity and cerebral palsy. Dev Med Child Neurol. 2016;58:7–11. doi: 10.1111/dmcn.13040. PubMed DOI PMC

CRITTENDEN JR, LACEY CJ, LEE T, BOWDEN HA, GRAYBIEL AM. Severe drug-induced repetitive behaviors and striatal overexpression of VAChT in ChAT-ChR2-EYFP BAC transgenic mice. Front Neural Circuits. 2014:8. doi: 10.3389/fncir.2014.00057. PubMed DOI PMC

CURTIS DJ, SOOD A, PHILLIPS TJ, LEINSTER VHL, NISHIGUCHI A, COYLE C, LACHARME-LORA L, BEAUMONT O, KEMP H, GOODALL R, CORNES L, GIUGLIANO M, BARONE RA, MATSUSAKI M, AKASHI M, TANAKA HY, KANO M, McGARVEY J, HALEMANI ND, SIMON K, KEEHAN R, IND W, MASTERS T, GRANT S, ATHWAL S, COLLETT G, TANNETTA D, SARGENT IL, SCULL-BROWN E, LIU X, AQUILINA K, COHEN N, LANE JD, THORESEN M, HANLEY J, RANDALL A, CASE CP. Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions. Exp Neurol. 2014;261:386–395. doi: 10.1016/j.expneurol.2014.05.003. PubMed DOI

De COURTEN-MYERS GM, XI G, HWANG JH, DUNN RS, MILLS AS, HOLLAND SK, WAGNER KR, MYERS RE. Hypoglycemic brain injury: potentiation from respiratory depression and injury aggravation from hyperglycemic treatment overshoots. J Cereb Blood Flow Metab. 2000;20:82–92. doi: 10.1097/00004647-200001000-00012. PubMed DOI

DELCOUR M, OLIVIER P, CHAMBON C, PANSIOT J, RUSSIER M, LIBERGE M, XIN D, GESTREAU C, ALESCIO-LAUTIER B, GRESSENS P, VERNEY C, BARBE MF, BAUD O, COQ J-O. Neuroanatomical, sensorimotor and cognitive deficits in adult rats with white matter injury following prenatal ischemia: Brain dysfunctions after gestational ischemia. Brain Pathol. 2012;22:1–16. doi: 10.1111/j.1750-3639.2011.00504.x. PubMed DOI PMC

DELCOUR M, RUSSIER M, XIN DL, MASSICOTTE VS, BARBE MF, COQ J-O. Mild musculoskeletal and locomotor alterations in adult rats with white matter injury following prenatal ischemia. Int J Dev Neurosci. 2011;29:593–607. doi: 10.1016/j.ijdevneu.2011.02.010. PubMed DOI

DELGADO M, GANEA D. Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma. FASEB J. 2003;17:1922–1924. doi: 10.1096/fj.02-1029fje. PubMed DOI

DERRICK M. Preterm fetal hypoxia-ischemia causes hypertonia and motor deficits in the neonatal rabbit: A model for human cerebral palsy? J Neurosci. 2004;24:24–34. doi: 10.1523/JNEUROSCI.2816-03.2004. PubMed DOI PMC

DING H, ZHANG H, DING H, LI D, YI X, MA X, LI R, HUANG M, JU X. Transplantation of placenta-derived mesenchymal stem cells reduces hypoxic-ischemic brain damage in rats by ameliorating the inflammatory response. Cell Mol Immunol. 2017;14:693–701. doi: 10.1038/cmi.2015.99. PubMed DOI PMC

DING P, REN D, HE S, HE M, ZHANG G, CHEN Y, SANG H, PENG Z, YAN W. Sirt1 mediates improvement in cognitive defects induced by focal cerebral ischemia following hyperbaric oxygen preconditioning in rats. Physiol Res. 2017;66:1029–1039. doi: 10.33549/physiolres.933544. PubMed DOI

DIXON B, REIS C, HO W, TANG J, ZHANG J. Neuroprotective strategies after neonatal hypoxic ischemic encephalopathy. Int J Mol Sci. 2015;16:22368–22401. doi: 10.3390/ijms160922368. PubMed DOI PMC

DRAHOTA Z, MOUREK J, RAUCHOVÁ H, TROJAN S. Molecular and cellular mechanisms involved in the high resistance of neonatal brain to anoxia. In: GORROD JW, ALBANO O, FERRARI E, PAPA S, editors. Molecular Basis of Neurological Disorders and Their Treatment. Springer; Dordrecht: 1991. pp. 289–295.

DUBOVICKÝ M, UJHÁZY E, KOVACOVSKÝ P, NAVAROVÁ J, JURÁNI M, SOLTÉS L. Effect of melatonin on neurobehavioral dysfunctions induced by intrauterine hypoxia in rats. Cent Eur J Public Health. 2004;12(Suppl):S23–25. doi: 10.21101/cejph.b0099. PubMed DOI

DUBROVSKAYA NM, ZHURAVIN IA. Ontogenetic characteristics of behavior in rats subjected to hypoxia on day 14 or day 18 of embryogenesis. Neurosci Behav Physiol. 2010;40:231–238. doi: 10.1007/s11055-009-9235-2. PubMed DOI

ESIH K, GORIČAR K, DOLŽAN V, RENER-PRIMEC Z. Antioxidant polymorphisms do not influence the risk of epilepsy or its drug resistance after neonatal hypoxic-ischemic brain injury. Seizure. 2017;46:38–42. doi: 10.1016/j.seizure.2017.01.005. PubMed DOI

ESKILD A, STRØM-ROUM EM, HAAVALDSEN C. Does the biological response to fetal hypoxia involve angiogenesis, placental enlargement and preeclampsia? Paediatr Perinat Epidemiol. 2016;30:305–309. doi: 10.1111/ppe.12283. PubMed DOI PMC

FAN H, LI X, WANG W, LAI Q, TANG X, GAO D, YIN X, XU T. Effects of NMDA-receptor antagonist on the expressions of bcl-2 and bax in the subventricular zone of neonatal rats with hypoxia-ischemia brain damage. Cell Biochem Biophys. 2015;73:323–330. doi: 10.1007/s12013-015-0586-8. PubMed DOI

FOLKERTH RD. Periventricular leukomalacia: overview and recent findings. Pediatr Dev Pathol. 2006;9:3–13. doi: 10.2350/06-01-0024.1. PubMed DOI

GABRIELOVÁ E, KŘEN V, JABŮREK M, MODRIANSKÝ M. Silymarin component 2,3-dehydrosilybin attenuates cardiomyocyte damage following hypoxia/reoxygenation by limiting oxidative stress. Physiol Res. 2015;64:79–91. PubMed

GADIROVA LB, AGAEV TM. Activity of phosphate-dependent glutaminase in the brain of rats exposed to prenatal hypoxia during organogenesis. Bull Exp Biol Med. 2015;160:187–189. doi: 10.1007/s10517-015-3123-2. PubMed DOI

GIZA CC, PRINS ML. Is being plastic fantastic? Mechanisms of altered plasticity after developmental traumatic brain injury. Dev Neurosci. 2006;28:364–379. doi: 10.1159/000094163. PubMed DOI PMC

GLASS HC, HONG KJ, ROGERS EE, JEREMY RJ, BONIFACIO SL, SULLIVAN JE, BARKOVICH AJ, FERRIERO DM. Risk factors for epilepsy in children with neonatal encephalopathy. Pediatr Res. 2011;70:535–540. doi: 10.1203/PDR.0b013e31822f24c7. PubMed DOI PMC

GOLAN MH, MANE R, MOLCZADZKI G, ZUCKERMAN M, KAPLAN-LOUSON V, HULEIHEL M, PEREZ-POLO JR. Impaired migration signaling in the hippocampus following prenatal hypoxia. Neuropharmacology. 2009;57:511–522. doi: 10.1016/j.neuropharm.2009.07.028. PubMed DOI

GONZALEZ-RODRIGUEZ PJ, XIONG F, LI Y, ZHOU J, ZHANG L. Fetal hypoxia increases vulnerability of hypoxic-ischemic brain injury in neonatal rats: Role of glucocorticoid receptors. Neurobiol Dis. 2014;65:172–179. doi: 10.1016/j.nbd.2014.01.020. PubMed DOI PMC

GUZMAN MS, De JAEGER X, RAULIC S, SOUZA IA, LI AX, SCHMID S, MENON RS, GAINETDINOV RR, CARON MG, BARTHA R, PRADO VF, PRADO MAM. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission. PLoS Biol. 2011;9:e1001194. doi: 10.1371/journal.pbio.1001194. PubMed DOI PMC

HANISCH U-K, KETTENMANN H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10:1387–1394. doi: 10.1038/nn1997. PubMed DOI

HASSELMO ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006;16:710–715. doi: 10.1016/j.conb.2006.09.002. PubMed DOI PMC

HEFTER D, MARTI HH, GASS P, INTA D. Perinatal hypoxia and ischemia in animal models of schizophrenia. Front Psychiatry. 2018:9. doi: 10.3389/fpsyt.2018.00106. PubMed DOI PMC

HERLENIUS E, LAGERCRANTZ H. Development of neurotransmitter systems during critical periods. Exp Neurol. 2004;190:8–21. doi: 10.1016/j.expneurol.2004.03.027. PubMed DOI

HERMANS RH, HUNTER DE, McGIVERN RF, CAIN CD, LONGO LD. Behavioral sequelae in young rats of acute intermittent antenatal hypoxia. Neurotoxicol Teratol. 1992;14:119–129. doi: 10.1016/0892-0362(92)90060-N. PubMed DOI

HOEGER H, ENGELMANN M, BERNERT G, SEIDL R, BUBNA-LITTITZ H, MOSGOELLER W, LUBEC B, LUBEC G. Long term neurological and behavioral effects of graded perinatal asphyxia in the rat. Life Sci. 2000;66:947–962. doi: 10.1016/S0024-3205(99)00678-5. PubMed DOI

HOWELL KR, PILLAI A. Effects of prenatal hypoxia on schizophrenia-related phenotypes in heterozygous reeler mice: A gene×environment interaction study. Eur Neuropsychopharmacol. 2014;24:1324–1336. doi: 10.1016/j.euroneuro.2014.05.011. PubMed DOI PMC

JAIN V, CHARI R, MASLOVITZ S, FARINE D, BUJOLD E, GAGNON R, BASSO M, BOS H, BROWN R, COOPER S, GOUIN K, McLEOD NL, MENTICOGLOU S, MUNDLE W, PYLYPJUK C, ROGGENSACK A, SANDERSON F MATERNAL FETAL MEDICINE COMMITTEE. Guidelines for the management of a pregnant trauma patient. J Obstet Gynaecol Can. 2015;37:553–574. doi: 10.1016/S1701-2163(15)30232-2. PubMed DOI

JANSSON T, POWELL TL. Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clin Sci (Lond) 2007;113:1–13. doi: 10.1042/CS20060339. PubMed DOI

JOHNSTON MV, FERRIERO DM, VANNUCCI SJ, HAGBERG H. Models of cerebral palsy: which ones are best? J Child Neurol. 2005;20:984–987. doi: 10.1177/08830738050200121001. PubMed DOI

KAUR C, SIVAKUMAR V, LU J, TANG FR, LING EA. Melatonin attenuates hypoxia-induced ultrastructural changes and increased vascular permeability in the developing hippocampus. Brain Pathol. 2008;18:533–547. doi: 10.1111/j.1750-3639.2008.00156.x. PubMed DOI PMC

KHASHABA MT, SHOUMAN BO, SHALTOUT AA, AL-MARSAFAWY HM, ABDEL-AZIZ MM, PATEL K, ALY H. Excitatory amino acids and magnesium sulfate in neonatal asphyxia. Brain Dev. 2006;28:375–379. doi: 10.1016/j.braindev.2005.11.010. PubMed DOI

KIMBALL R, WAYMENT M, MERRILL D, WAHLQUIST T, REYNOLDS PR, ARROYO JA. Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR) Physiol Rep. 2015;3:e12651. doi: 10.14814/phy2.12651. PubMed DOI PMC

KOUNDAL S, GANDHI S, KAUR T, KHUSHU S. Neurometabolic and structural alterations in rat brain due to acute hypobaric hypoxia: in vivo 1H MRS at 7T: Neurometabolic alterations due to acute hypobaric hypoxia. NMR Biomed. 2014;27:341–347. doi: 10.1002/nbm.3068. PubMed DOI

LANDRY JP, HAWKINS C, WIEBE S, BALABAN E, POMPEIANO M. Opposing effects of hypoxia on catecholaminergic locus coeruleus and hypocretin/orexin neurons in chick embryos: Hypoxia and arousal in chick embryos. Dev Neurobiol. 2014;74:1030–1037. doi: 10.1002/dneu.22182. PubMed DOI

LEVITINA EV. Effect of mexidol on clinical and biochemical parameters of perinatal hypoxia in newborn children] Eksp Klin Farmakol. 2001;64:34–36. PubMed

LI T, LUO Z, LIU Y, WANG M, YU X, CAO C, LIAO Z, DING Y, YUE S. Excessive activation of NMDA receptors induced neurodevelopmental brain damage and cognitive deficits in rats exposed to intrauterine hypoxia. Neurochem Res. 2018;43:566–580. doi: 10.1007/s11064-017-2451-1. PubMed DOI

LIM JH, LEE YM, CHUN YS, CHEN J, KIM JE, PARK JW. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 2010;38:864–878. doi: 10.1016/j.molcel.2010.05.023. PubMed DOI

LIU W, CHEN O, CHEN C, WU B, TANG J, ZHANG JH. Protective effects of hydrogen on fetal brain injury during maternal hypoxia. In: ZHANG J, COLOHAN A, editors. Intracerebral hemorrhage research. Vienna, Springer; Vienna: 2011. pp. 307–311. PubMed DOI PMC

MACH M, DUBOVICKÝ M, NAVAROVÁ J, KOVACOVSKÝ P, UJHÁZY E. Vitamin E supplementation in phenytoin induced developmental toxicity in rats: postnatal study. Neuro Endocrinol Lett. 2006; 27(Suppl 2):69–73. PubMed

MARESOVÁ D, VALKOUNOVÁ I, JANDOVÁ K, BORTELOVÁ J, TROJAN S. Excitability changes of cortical neurons during the postnatal period in rats exposed to prenatal hypobaric hypoxia. Physiol Res. 2001;50:215–219. PubMed

McCLENDON E, CHEN K, GONG X, SHARIFNIA E, HAGEN M, CAI V, SHAVER DC, RIDDLE A, DEAN JM, GUNN AJ, MOHR C, KAPLAN JS, ROSSI DJ, KROENKE CD, HOHIMER AR, BACK SA. Prenatal cerebral ischemia triggers dysmaturation of caudate projection neurons: Neuron Dysmaturation. Ann Neurol. 2014;75:508–524. doi: 10.1002/ana.24100. PubMed DOI PMC

McCLENDON E, SHAVER DC, DEGENER-O’BRIEN K, GONG X, NGUYEN T, HOERDER-SUABEDISSEN A, MOLNÁR Z, MOHR C, RICHARDSON BD, ROSSI DJ, BACK SA. Transient hypoxemia chronically disrupts maturation of preterm fetal ovine subplate neuron arborization and activity. J Neurosci. 2017;37:11912–11929. doi: 10.1523/JNEUROSCI.2396-17.2017. PubMed DOI PMC

McGUIRE W. Perinatal asphyxia. BMJ Clin Evid. 2007 2007. PubMed PMC

MUNDKUR N. Neuroplasticity in children. Indian J Pediatr. 2005;72:855–857. doi: 10.1007/BF02731115. PubMed DOI

MYERS RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol. 1972;112:246–276. doi: 10.1016/0002-9378(72)90124-X. PubMed DOI

NIAN M. Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 2004;94:1543–1553. doi: 10.1161/01.RES.0000130526.20854.fa. PubMed DOI

OH C, DONG Y, LIU H, THOMPSON LP. Intrauterine hypoxia upregulates proinflammatory cytokines and matrix metalloproteinases in fetal guinea pig hearts. Am J Obstet Gynecol. 2008;199:78.e1–78.e6. doi: 10.1016/j.ajog.2007.12.004. PubMed DOI

PATTERSON AJ, ZHANG L. Hypoxia and fetal heart development. Curr Mol Med. 2010;10:653–666. doi: 10.2174/156652410792630643. PubMed DOI PMC

PERRIN D, MAMET J, SCARNA H, ROUX JC, BÉROD A, DALMAZ Y. Long-term prenatal hypoxia alters maturation of brain catecholaminergic systems and motor behavior in rats. Synap N Y N. 2004;54:92–101. doi: 10.1002/syn.20065. PubMed DOI

POYTON RO, BALL KA, CASTELLO PR. Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab. 2009;20:332–340. doi: 10.1016/j.tem.2009.04.001. PubMed DOI

RAČEK A, BEŇOVÁ K, ARNOUL P, ZÁVODSKÁ M, ANGELIDIS A, CIGÁNKOVÁ V, ŠIMAIOVÁ V, RAČEKOVÁ E. Age-dependent effect of long-term microwave radiation on postnatal neurogenesis in rats. morphological and behavioral study. Physiol Res. 2018;67:495–503. doi: 10.33549/physiolres.933752. PubMed DOI

RAMAN L, TKAC I, ENNIS K, GEORGIEFF MK, GRUETTER R, RAO R. In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus. Dev Brain Res. 2005;156:202–209. doi: 10.1016/j.devbrainres.2005.02.013. PubMed DOI

RILJAK V, KRAF J, DARYANANI A, JIRUŠKA P, OTÁHAL J. Pathophysiology of perinatal hypoxic-ischemic encephalopathy - biomarkers, animal models and treatment perspectives. Physiol Res. 2016;65(Suppl 5):S533–S545. doi: 10.33549/physiolres.933541. PubMed DOI

ROBINSON S, PETELENZ K, LI Q, COHEN ML, DECHANT A, TABRIZI N, BUCEK M, LUST D, MILLER RH. Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats. Neurobiol Dis. 2005;18:568–581. doi: 10.1016/j.nbd.2004.10.024. PubMed DOI

ROCHA-FERREIRA E, HRISTOVA M. Plasticity in the neonatal brain following hypoxic-ischaemic injury. Neural Plast. 2016;2016:4901014. doi: 10.1155/2016/4901014. PubMed DOI PMC

RONG GUO, WEIJIAN HOU, YAFENG DONG, ZHIYONG YU, STITES J, WEINER CP. Brain injury caused by chronic fetal hypoxemia is mediated by inflammatory cascade activation. Reprod Sci. 2010;17:540–548. doi: 10.1177/1933719110364061. PubMed DOI

SAB IM, FERRAZ MMD, AMARAL TAS, RESENDE AC, FERRAZ MR, MATSUURA C, BRUNINI TMC, MENDES-RIBEIRO AC. Prenatal hypoxia, habituation memory and oxidative stress. Pharmacol Biochem Behav. 2013;107:24–28. doi: 10.1016/j.pbb.2013.04.004. PubMed DOI

SANDAU US, HANDA RJ. Glucocorticoids exacerbate hypoxia-induced expression of the pro-apoptotic gene Bnip3 in the developing cortex. Neuroscience. 2007;144:482–494. doi: 10.1016/j.neuroscience.2006.10.003. PubMed DOI PMC

SAVIGNON T, COSTA E, TENORIO F, MANHÃES AC, BARRADAS PC. Prenatal hypoxic-ischemic insult changes the distribution and number of NADPH-diaphorase cells in the cerebellum. PloS One. 2012;7:e35786. doi: 10.1371/journal.pone.0035786. PubMed DOI PMC

SEDLÁČKOVÁ N, KRAJČIOVÁ M, KOPRDOVÁ R, UJHÁZY E, BRUCKNEROVÁ I, MACH M. Subchronic perinatal asphyxia increased anxiety-and depression-like behaviors in the rat offspring. Neuro Endocrinol Lett. 2014;35(Suppl 2):214–220. PubMed

SIMONOVÁ Z, STERBOVÁ K, BROZEK G, KOMÁREK V, SYKOVÁ E. Postnatal hypobaric hypoxia in rats impairs water maze learning and the morphology of neurones and macroglia in cortex and hippocampus. Behav Brain Res. 2003;141:195–205. doi: 10.1016/S0166-4328(02)00366-2. PubMed DOI

TAKADA SH, DOS SANTOS HAEMMERLE CA, MOTTA-TEIXEIRA LC, MACHADO-NILS AV, LEE VY, TAKASE LF, CRUZ-RIZZOLO RJ, KIHARA AH, XAVIER GF, WATANABE I-S, NOGUEIRA MI. Neonatal anoxia in rats: hippocampal cellular and subcellular changes related to cell death and spatial memory. Neuroscience. 2015;284:247–259. doi: 10.1016/j.neuroscience.2014.08.054. PubMed DOI

TRAYNELIS SF, WOLLMUTH LP, MCBAIN CJ, MENNITI FS, VANCE KM, OGDEN KK, HANSEN KB, YUAN H, MYERS SJ, DINGLEDINE R. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. 2010;62:405–496. doi: 10.1124/pr.109.002451. PubMed DOI PMC

TYULKOVA EI, VATAEVA LA, VETROVOY OV, ROMANOVSKY DY. [Prenatal hypoxia modifies working memory and the activity of hippocampal polyphosphoinositide system in rats] Zh Evol Biokhim Fiziol. 2015;51:115–121. doi: 10.1134/S0022093015020064. PubMed DOI

UJHAZY E, DUBOVICKY M, NAVAROVA J, SEDLACKOVA N, DANIHEL L, BRUCKNEROVA I, MACH M. Subchronic perinatal asphyxia in rats: Embryo-foetal assessment of a new model of oxidative stress during critical period of development. Food Chem Toxicol. 2013;61:233–239. doi: 10.1016/j.fct.2013.07.023. PubMed DOI

VANNUCCI RC, VANNUCCI SJ. Perinatal hypoxic-ischemic brain damage: evolution of an animal model. Dev Neurosci. 2005;27:81–86. doi: 10.1159/000085978. PubMed DOI

VLASSAKS E, GAVILANES AWD, VLES JSH, DEVILLE S, KRAMER BW, STRACKX E, MARTINEZ-MARTINEZ P. The effects of fetal and perinatal asphyxia on neuronal cytokine levels and ceramide metabolism in adulthood. J Neuroimmunol. 2013;255:97–101. doi: 10.1016/j.jneuroim.2012.09.011. PubMed DOI

WANG H, DÁVILA-GARCÍA MI, YARL W, GONDRÉ-LEWIS MC. Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus. Neuroscience. 2011;188:168–181. doi: 10.1016/j.neuroscience.2011.04.069. PubMed DOI PMC

WANG W-T, LEE P, DONG Y, YEH H-W, KIM J, WEINER CP, BROOKS WM, CHOI I-Y. In vivo neurochemical characterization of developing guinea pigs and the effect of chronic fetal hypoxia. Neurochem Res. 2016;41:1831–1843. doi: 10.1007/s11064-016-1924-y. PubMed DOI

WEITZDOERFER R, GERSTL N, POLLAK D, HOEGER H, DREHER W, LUBEC G. Long-term influence of perinatal asphyxia on the social behavior in aging rats. Gerontology. 2004;50:200–205. doi: 10.1159/000078348. PubMed DOI

XUE B, MAO L-M, JIN D-Z, WANG JQ. Regulation of synaptic MAPK/ERK phosphorylation in the rat striatum and medial prefrontal cortex by dopamine and muscarinic acetylcholine receptors: Synaptic ERK Phosphorylation. J Neurosci Res. 2015;93:1592–1599. doi: 10.1002/jnr.23622. PubMed DOI PMC

ZHANG X, LI L, ZHANG X, XIE W, LI L, YANG D, HENG X, DU Y, DOODY RS, LE W. Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer’s disease neuropathology in APPSwe/PS1A246E transgenic mice. Neurobiol Aging. 2013;34:663–678. doi: 10.1016/j.neurobiolaging.2012.06.012. PubMed DOI

ZHENG Y, WANG X-M. Expression changes in lactate and glucose metabolism and associated transporters in basal ganglia following hypoxic-ischemic reperfusion injury in piglets. AJNR Am J Neuroradiol. 2018;39:569–576. doi: 10.3174/ajnr.A5505. PubMed DOI PMC

The GluN2B-Containing NMDA Receptor Alleviates Neuronal Apoptosis in Neonatal Hypoxic-Ischemic Encephalopathy by Activating PI3K-Akt-CREB Signaling Pathwa

Impact of prenatal hypoxia on the development and behavior of the rat offspring

Rare causes of respiratory insufficiency in newborns