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Perinatal hypoxic-ischemic damage: review of the current treatment possibilities

. 2020 Dec 31 ; 69 (Suppl 3) : S379-S401.

Language English Country Czech Republic Media print

Document type Journal Article, Review

Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.

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ALLEN KA, BRANDON DH. Hypoxic ischemic encephalopathy: pathophysiology and experimental treatments. Newborn Infant Nurs Rev. 2011;11:125–133. doi: 10.1053/j.nainr.2011.07.004. PubMed DOI PMC

ALSINA M, MARTÍN-ANCEL A, ALARCON-ALLEN A, ARCA G, GAYÁ F, GARCÍA-ALIX A. The severity of hypoxic-ischemic encephalopathy correlates with multiple organ dysfunction in the hypothermia era. Pediatr Crit Care Med. 2017;18:234–240. doi: 10.1097/PCC.0000000000001068. PubMed DOI

ALTAMENTOVA S, RUMAJOGEE P, HONG J, BELDICK SR, PARK SJ, YEE A, FEHLINGS MG. Methylprednisolone reduces persistent post-ischemic inflammation in a rat hypoxia-ischemia model of perinatal stroke. Transl Stroke Res. 2020:1117–1136. doi: 10.1007/s12975-020-00792-2. PubMed DOI

ALVAREZ FJ, LAFUENTE H, REY-SANTANO MC, MIELGO VE, GASTIASORO E, RUEDA M, PERTWEE RG, CASTILLO AI, ROMERO J, MARTINEZ-ORGADO J. Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets. Pediatr Res. 2008;64:653–658. doi: 10.1203/PDR.0b013e318186e5dd. PubMed DOI

ALY H, ELMAHDY H, EL-DIB M, ROWISHA M, AWNY M, EL-GOHARY T, ELBATCH M, HAMISA M, EL-MASHAD A. Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. J Perinatol. 2015;35:186–191. doi: 10.1038/jp.2014.186. PubMed DOI

AMANTEA D, CERTO M, PETRELLI F, TASSORELLI C, MICIELI G, CORASANITI MT, PUCCETTI P, FALLARINO F, BAGETTA G. Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype. Exp Neurol. 2016;275:116–125. doi: 10.1016/j.expneurol.2015.10.012. PubMed DOI

AMER AR, OORSCHOT DE. Xenon combined with hypothermia in perinatal hypoxic-ischemic encephalopathy: a noble gas, a noble mission. Pediatr Neurol. 2018;84:5–10. doi: 10.1016/j.pediatrneurol.2018.02.009. PubMed DOI

ANNA R, ROLF R, MARK C. Update of the organoprotective properties of xenon and argon: from bench to beside. Intensive Care Med Exp. 2020;8:11. doi: 10.1186/s40635-020-0294-6. PubMed DOI PMC

ARTEAGA O, ÁLVAREZ A, REVUELTA M, SANTAOLALLA F, URTASUN A, HILARIO E. Role of antioxidants in neonatal hypoxic-ischemic brain injury: new therapeutic approaches. Int J Mol Sci. 2017;18:265. doi: 10.3390/ijms18020265. PubMed DOI PMC

ARTEAGA O, REVUELTA M, URIGÜEN L, ALVAREZ A, MONTALVO H, HILARIO E. Pretreatment with resveratrol prevents neuronal injury and cognitive deficits induced by perinatal hypoxia-ischemia in rats. PLoS One. 2015;10:e0142424. doi: 10.1371/journal.pone.0142424. PubMed DOI PMC

AZZOPARDI D, ROBERTSON NJ, BAINBRIDGE A, CADY E, CHARLES-EDWARDS G, DEIERL A, FAGIOLO G, FRANKS NP, GRIFFITHS J, HAJNAL J. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. Lancet Neurol. 2016;15:145–153. doi: 10.1016/S1474-4422(15)00347-6. PubMed DOI PMC

BALLOUGH GP, CANN FJ, SMITH CD, FORSTER JS, KLING CE, FILBERT MG. GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage. Mol Chem Neuropathol. 1998;34:1–23. doi: 10.1007/BF02815133. PubMed DOI

BARKS JD, LIU Y, WANG L, PAI MP, SILVERSTEIN FS. Repurposing azithromycin for neonatal neuroprotection. Pediatr Res. 2019;86:444–451. doi: 10.1038/s41390-019-0408-6. PubMed DOI PMC

BASSAN M, ZAMOSTIANO R, DAVIDSON A, PINHASOV A, GILADI E, PERL O, BASSAN H, BLAT C, GIBNEY G, GLAZNER G. Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem. 1999;72:1283–1293. doi: 10.1046/j.1471-4159.1999.0721283.x. PubMed DOI

BASTIANETTO S, MÉNARD C, QUIRION R. Neuroprotective action of resveratrol. Biochim Biophys Acta. 2015;1852:1195–1201. doi: 10.1016/j.bbadis.2014.09.011. PubMed DOI

BAYDAS G, REITER RJ, AKBULUT M, TUZCU M, TAMER S. Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels. Neuroscience. 2005;135:879–886. doi: 10.1016/j.neuroscience.2005.05.048. PubMed DOI

BENDERS MJ, BOS AF, RADEMAKER CM, RIJKEN M, TORRANCE HL, GROENENDAAL F, Van BEL F. Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia. Arch Dis Child Fetal Neonatal Ed. 2006;91:F163–F165. doi: 10.1136/adc.2005.086652. PubMed DOI PMC

BERMAN DR, MOZURKEWICH E, LIU Y, SHANGGUAN Y, BARKS JD, SILVERSTEIN FS. Docosahexaenoic acid augments hypothermic neuroprotection in a neonatal rat asphyxia model. Neonatology. 2013;104:71–78. doi: 10.1159/000351011. PubMed DOI PMC

BERNAUDIN M, MARTI HH, ROUSSEL S, DIVOUX D, NOUVELOT A, MacKENZIE ET, PETIT E. A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab. 1999;19:643–651. doi: 10.1097/00004647-199906000-00007. PubMed DOI

BJÖRKLUND LM, SÁNCHEZ-PERNAUTE R, CHUNG S, ANDERSSON T, CHEN IYC, McNAUGHT KSP, BROWNELL A-L, JENKINS BG, WAHLESTEDT C, KIM K-S, ISACSON O. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A. 2002;99:2344–2349. doi: 10.1073/pnas.022438099. PubMed DOI PMC

BONESTROO HJ, NIJBOER CH, Van VELTHOVEN CT, Van BEL F, HEIJNEN CJ. The neonatal brain is not protected by osteopontin peptide treatment after hypoxia-ischemia. Dev Neurosci. 2015;37:142–152. doi: 10.1159/000369093. PubMed DOI

BRINES ML, GHEZZI P, KEENAN S, AGNELLO D, De LANEROLLE NC, CERAMI C, ITRI LM, CERAMI A. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A. 2000;97:10526–10531. doi: 10.1073/pnas.97.19.10526. PubMed DOI PMC

BROAD KD, FIERENS I, FLEISS B, ROCHA-FERREIRA E, EZZATI M, HASSELL J, ALONSO-ALCONADA D, BAINBRIDGE A, KAWANO G, MA D. Inhaled 45–50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia. Neurobiol Dis. 2016;87:29–38. doi: 10.1016/j.nbd.2015.12.001. PubMed DOI PMC

BUTLER WT. The nature and significance of osteopontin. Connect Tissue Res. 1989;23:123–136. doi: 10.3109/03008208909002412. PubMed DOI

CAMPOS-PIRES R, ARMSTRONG SP, SEBASTIANI A, LUH C, GRUSS M, RADYUSHKIN K, HIRNET T, WERNER C, ENGELHARD K, FRANKS NP, THAL SC, DICKINSON R. Xenon improves neurologic outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury. Crit Care Med. 2015;43:149–158. doi: 10.1097/CCM.0000000000000624. PubMed DOI PMC

CARLONI S, PERRONE S, BUONOCORE G, LONGINI M, PROIETTI F, BALDUINI W. Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J Pineal Res. 2008;44:157–164. doi: 10.1111/j.1600-079X.2007.00503.x. PubMed DOI

CASTILLO-MELENDEZ M, YAWNO T, JENKIN G, MILLER SL. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells. Front Neurosci. 2013;7:194. doi: 10.3389/fnins.2013.00194. PubMed DOI PMC

CETINKAYA M, ALKAN T, OZYENER F, KAFA IM, KURT MA, KOKSAL N. Possible neuroprotective effects of magnesium sulfate and melatonin as both pre-and post-treatment in a neonatal hypoxic-ischemic rat model. Neonatology. 2011;99:302–310. doi: 10.1159/000320643. PubMed DOI

CHANG YS, AHN SY, SUNG S, PARK WS. Stem cell therapy for neonatal disorders: prospects and challenges. Yonsei Med J. 2017;58:266–271. doi: 10.3349/ymj.2017.58.2.266. PubMed DOI PMC

CHIU LS, ANDERTON RS, KNUCKEY NW, MELONI BP. Peptide pharmacological approaches to treating traumatic brain injury: a case for arginine-rich peptides. Mol Neurobiol. 2017;54:7838–7857. doi: 10.1007/s12035-016-0287-3. PubMed DOI

CHOI HA, BADJATIA N, MAYER SA. Hypothermia for acute brain injury-mechanisms and practical aspects. Nat Rev Neurol. 2012;8:214. doi: 10.1038/nrneurol.2012.21. PubMed DOI

CHUNG S, SHIN BS, HEDLUND E, PRUSZAK J, FERREE A, KANG UJ, ISACSON O, KIM KS. Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation. J Neurochem. 2006;97:1467–1480. doi: 10.1111/j.1471-4159.2006.03841.x. PubMed DOI PMC

COLELLA M, BIRAN V, BAUD O. Melatonin and the newborn brain. Early Hum Dev. 2016;102:1–3. doi: 10.1016/j.earlhumdev.2016.09.001. PubMed DOI

CONCEPCION KR, ZHANG L. Corticosteroids and perinatal hypoxic-ischemic brain injury. Drug Discov Today. 2018;23:1718–1732. doi: 10.1016/j.drudis.2018.05.019. PubMed DOI PMC

COOPER SD, FELKINS K, BAKER TE, HALE TW. Transfer of methylprednisolone into breast milk in a mother with multiple sclerosis. J Hum Lact. 2015;31:237–239. doi: 10.1177/0890334415570970. PubMed DOI

COTTEN CM, SHANKARAN S. Hypothermia for hypoxic-ischemic encephalopathy. Expert Rev Obstet Gynecol. 2010;5:227–239. doi: 10.1586/eog.10.7. PubMed DOI PMC

DAMMANN O, FERRIERO D, GRESSENS P. Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters. Pediatr Res. 2011;70:1–2. doi: 10.1203/PDR.0b013e318223f38d. PubMed DOI

DANEYEMEZ M, KURT E, COSAR A, YUCE E, IDE T. Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage in rats. Neuroscience. 1999;92:693–697. doi: 10.1016/S0306-4522(99)00038-X. PubMed DOI

DANIELYAN L, SCHÄFER R, Von AMELN-MAYERHOFER A, BUADZE M, GEISLER J, KLOPFER T, BURKHARDT U, PROKSCH B, VERLEYSDONK S, AYTURAN M. Intranasal delivery of cells to the brain. Eur J Cell Biol. 2009;88:315–324. doi: 10.1016/j.ejcb.2009.02.001. PubMed DOI

DAVIDSON JO, WASSINK G, Van den HEUIJ LG, BENNET L, GUNN AJ. Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy - where to from here? Front Neurol. 2015;6 doi: 10.3389/fneur.2015.00198. PubMed DOI PMC

DEYKUN K, POMETLOVA M, SCHUTOVA B, MARES J. Modulations of behavioral consequences of minor cortical ischemic lesion by application of free radicals scavengers. Gen Physiol Biophys. 2011;30:263–270. doi: 10.4149/gpb_2011_03_263. PubMed DOI

DICOU E, ATTOUB S, GRESSENS P. Neuroprotective effects of leptin in vivo and in vitro. Neuroreport. 2001;12:3947–3951. doi: 10.1097/00001756-200112210-00019. PubMed DOI

DIXON BJ, CHEN D, ZHANG Y, FLORES J, MALAGUIT J, NOWRANGI D, ZHANG JH, TANG J. Intranasal administration of interferon beta attenuates neuronal apoptosis via the JAK1/STAT3/BCL-2 pathway in a rat model of neonatal hypoxic-ischemic encephalopathy. ASN Neuro. 2016;8:1759091416670492. doi: 10.1177/1759091416670492. PubMed DOI PMC

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

DOUGLAS-ESCOBAR M, WEISS MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015;169:397–403. doi: 10.1001/jamapediatrics.2014.3269. PubMed DOI

DYALL SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52. doi: 10.3389/fnagi.2015.00052. PubMed DOI PMC

EDWARDS AD, BROCKLEHURST P, GUNN AJ, HALLIDAY H, JUSZCZAK E, LEVENE M, STROHM B, THORESEN M, WHITELAW A, AZZOPARDI D. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010;340:c363. doi: 10.1136/bmj.c363. PubMed DOI PMC

ERGENEKON E. Therapeutic hypothermia in neonatal intensive care unit: challenges and practical points. J Clin Neonatol. 2016;5:8–17. doi: 10.4103/2249-4847.173271. DOI

ESPOSITO E, CUZZOCREA S. Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol. 2010;8:228–242. doi: 10.2174/157015910792246155. PubMed DOI PMC

FARKHONDEH T, FOLGADO SL, POURBAGHER-SHAHRI AM, ASHRAFIZADEH M, SAMARGHANDIAN S. The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway. Biomed Pharmacother. 2020;127:110234. doi: 10.1016/j.biopha.2020.110234. PubMed DOI

FENG EC, JIANG L. Effects of leptin on neurocognitive and motor functions in juvenile rats in a preterm brain damage model. Mol Med Rep. 2018;18:4095–4102. doi: 10.3892/mmr.2018.9389. PubMed DOI

FERNÁNDEZ-LÓPEZ D, PRADILLO JM, GARCÍA-YÉBENES I, MARTÍNEZ-ORGADO JA, MORO MA, LIZASOAIN I. The cannabinoid WIN55212-2 promotes neural repair after neonatal hypoxia-ischemia. Stroke. 2010;41:2956–2964. doi: 10.1161/STROKEAHA.110.599357. PubMed DOI

FERRARI G, ANDERSON BL, STEPHENS RM, KAPLAN DR, GREENE LA. Prevention of apoptotic neuronal death by GM1 ganglioside. J Biol Chem. 1995;270:3074–3080. doi: 10.1074/jbc.270.7.3074. PubMed DOI

FILIPPI L, FIORINI P, CATARZI S, BERTI E, PADRINI L, LANDUCCI E, DONZELLI G, BARTALENA L, FIORENTINI E, BOLDRINI A, GIAMPIETRI M, SCARAMUZZO RT, La MARCA G, DELLA BONA ML, FIORI S, TINELLI F, BANCALE A, GUZZETTA A, CIONI G, PISANO T, FALCHI M, GUERRINI R. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study. J Matern Fetal Neonatal Med. 2018;31:973–980. doi: 10.1080/14767058.2017.1304536. PubMed DOI

GALINSKY R, DEAN JM, LINGAM I, ROBERTSON NJ, MALLARD C, BENNET L, GUNN AJ. A systematic review of magnesium sulfate for perinatal neuroprotection: what have we learnt from the past decade? Front Neurol. 2020;11:449. doi: 10.3389/fneur.2020.00449. PubMed DOI PMC

GAO Y, FU R, WANG J, YANG X, WEN L, FENG J. Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway. Pharm Biol. 2018;56:440–449. doi: 10.1080/13880209.2018.1502326. PubMed DOI PMC

GARBERG HT, SOLBERG R, BARLINN J, MARTINEZ-ORGADO J, LØBERG E-M, SAUGSTAD OD. High-dose cannabidiol induced hypotension after global hypoxia-ischemia in piglets. Neonatology. 2017;112:143–149. doi: 10.1159/000471786. PubMed DOI

GARG B, SHARMA D, BANSAL A. Systematic review seeking erythropoietin role for neuroprotection in neonates with hypoxic ischemic encephalopathy: presently where do we stand. J Matern Fetal Neonatal Med. 2018;31:3214–3224. doi: 10.1080/14767058.2017.1366982. PubMed DOI

GILBERT GL, KIM HJ, WAATAJA JJ, THAYER SA. Δ9-Tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. Brain Res. 2007;1128:61–69. doi: 10.1016/j.brainres.2006.03.011. PubMed DOI

GLAZNER GW, BOLAND A, DRESSE AE, BRENNEMAN DE, GOZES I, MATTSON MP. Activity-dependent neurotrophic factor peptide (ADNF9) protects neurons against oxidative stress-induced death. J Neurochem. 1999;73:2341–2347. doi: 10.1046/j.1471-4159.1999.0732341.x. PubMed DOI

GREGGIO S, De PAULA S, De OLIVEIRA IM, TRINDADE C, ROSA RM, HENRIQUES JAP, DACOSTA JC. NAP prevents acute cerebral oxidative stress and protects against long-term brain injury and cognitive impairment in a model of neonatal hypoxia-ischemia. Neurobiol Dis. 2011;44:152–159. doi: 10.1016/j.nbd.2011.06.018. PubMed DOI

GUPTA Y, GUPTA M, KOHLI K. Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J Physiol Pharmacol. 2003;47:373–386. PubMed

HALL ED. Methylprednisolone for the treatment of patients with acute spinal cord injuries: A propensity score-matched cohort study from a Canadian multi-center spinal cord injury registry. J Neurotrauma. 2016;33:972–974. doi: 10.1089/neu.2016.4473. PubMed DOI

HANSON LR, ROEYTENBERG A, MARTINEZ PM, COPPES VG, SWEET DC, RAO RJ, MARTI DL, HOEKMAN JD, MATTHEWS RB, FREY WH. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J Pharmacol Exp Ther. 2009;330:679–686. doi: 10.1124/jpet.108.149807. PubMed DOI PMC

HOBBS C, THORESEN M, TUCKER A, AQUILINA K, CHAKKARAPANI E, DINGLEY J. Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke. 2008;39:1307–1313. doi: 10.1161/STROKEAHA.107.499822. PubMed DOI

HOFFMAN DJ, MARRO PJ, McGOWAN JE, MISHRA OP, DELIVORIA-PAPADOPOULOS M. Protective effect of MgSO4 infusion on NMDA receptor binding characteristics during cerebral cortical hypoxia in the newborn piglet. Brain Res. 1994;644:144–149. doi: 10.1016/0006-8993(94)90357-3. PubMed DOI

HU S, CHENG D, PENG D, TAN J, HUANG Y, CHEN C. Leptin attenuates cerebral ischemic injury in rats by modulating the mitochondrial electron transport chain via the mitochondrial STAT3 pathway. Brain Behav. 2019;9:e01200. doi: 10.1002/brb3.1200. PubMed DOI PMC

HUUN MU. PhD Thesis. 2019. Omega-3 Treatment in Hypoxicischemic Brain Injury: An Experimental Study in Newborn Piglets.

JACOBS SE, BERG M, HUNT R, TARNOW-MORDI WO, INDER TE, DAVIS PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;2013:CD003311. doi: 10.1002/14651858.CD003311.pub3. PubMed DOI PMC

JACOBS SE, MORLEY CJ, INDER TE, STEWART MJ, SMITH KR, McNAMARA PJ, WRIGHT IM, KIRPALANI HM, DARLOW BA, DOYLE LW. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165:692–700. doi: 10.1001/archpediatrics.2011.43. PubMed DOI

JANOWSKA J, SYPECKA J. Therapeutic strategies for leukodystrophic disorders resulting from perinatal asphyxia: focus on myelinating oligodendrocytes. Mol Neurobiol. 2018;55:4388–4402. doi: 10.1007/s12035-017-0647-7. PubMed DOI PMC

JATANA M, SINGH I, SINGH AK, JENKINS D. Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res. 2006;59:684–689. doi: 10.1203/01.pdr.0000215045.91122.44. PubMed DOI

JAWORSKA J, ZALEWSKA T, SYPECKA J, ZIEMKA-NALECZ M. Effect of the HDAC inhibitor, sodium butyrate, on neurogenesis in a rat model of neonatal hypoxia-ischemia: potential mechanism of action. Mol Neurobiol. 2019;56:6341–6370. doi: 10.1007/s12035-019-1518-1. PubMed DOI PMC

JAWORSKA J, ZIEMKA-NALECZ M, SYPECKA J, ZALEWSKA T. The potential neuroprotective role of a histone deacetylase inhibitor, sodium butyrate, after neonatal hypoxia-ischemia. J Neuroinflammation. 2017;14:34. doi: 10.1186/s12974-017-0807-8. PubMed DOI PMC

JAYALAKSHMI K, SAIRAM M, SINGH S, SHARMA S, ILAVAZHAGAN G, BANERJEE P. Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture. Brain Res. 2005;1046:97–104. doi: 10.1016/j.brainres.2005.03.054. PubMed DOI

JEREZ-CALERO A, SALVATIERRA-CUENCA MT, BENITEZ-FELIPONI Á, FERNÁNDEZ-MARÍN CE, NARBONA-LÓPEZ E, UBEROS-FERNÁNDEZ J, MUÑOZ-HOYOS A. Hypothermia plus melatonin in asphyctic newborns: a randomized-controlled pilot study. Pediatr Crit Care Med. 2020;21:647–655. doi: 10.1097/PCC.0000000000002346. PubMed DOI

JONES NM, KARDASHYAN L, CALLAWAY JK, LEE EM, BEART PM. Long-term functional and protective actions of preconditioning with hypoxia, cobalt chloride, and desferrioxamine against hypoxic-ischemic injury in neonatal rats. Pediatr Res. 2008;63:620–624. doi: 10.1203/PDR.0b013e31816d9117. PubMed DOI

JUUL SE, HARCUM J, LI Y, CHRISTENSEN RD. Erythropoietin is present in the cerebrospinal fluid of neonates. J Pediatr. 1997;130:428–430. doi: 10.1016/S0022-3476(97)70205-1. PubMed DOI

KAANDORP JJ, Van BEL F, VEEN S, DERKS JB, GROENENDAAL F, RIJKEN M, ROZE E, VENEMA MMU, RADEMAKER CM, BOS AF. Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials. Arch Dis Child Fetal Neonatal Ed. 2012;97:F162–F166. doi: 10.1136/archdischild-2011-300356. PubMed DOI

KAPLAN JM, YOUD ME, LODIE TA. Immunomodulatory activity of mesenchymal stem cells. Curr Stem Cell Res Ther. 2011;6:297–316. doi: 10.2174/157488811797904353. PubMed DOI

KHAN M, SEKHON B, JATANA M, GIRI S, GILG AG, SEKHON C, SINGH I, SINGH AK. Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res. 2004;76:519–527. doi: 10.1002/jnr.20087. PubMed DOI

KIESEIER BC. The mechanism of action of interferon-β in relapsing multiple sclerosis. CNS Drugs. 2011;25:491–502. doi: 10.2165/11591110-000000000-00000. PubMed DOI

KLETKIEWICZ H, KLIMIUK M, WOŹNIAK A, MILA-KIERZENKOWSKA C, DOKLADNY K, ROGALSKA J. How to improve the antioxidant defense in asphyxiated newborns-lessons from animal models. Antioxidants (Basel) 2020;9:E898. doi: 10.3390/antiox9090898. PubMed DOI PMC

KLETKIEWICZ H, NOWAKOWSKA A, SIEJKA A, MILA-KIERZENKOWSKA C, WOŹNIAK A, CAPUTA M, ROGALSKA J. Deferoxamine improves antioxidative protection in the brain of neonatal rats: the role of anoxia and body temperature. Neurosci Lett. 2016;628:116–122. doi: 10.1016/j.neulet.2016.06.022. PubMed DOI

KUMRAL A, TUZUN F, YESILIRMAK D, DUMAN N, OZKAN H. Role of epigenetic regulatory mechanisms in neonatal hypoxic-ischemic brain injury. Med Hypotheses. 2009;72:692–693. doi: 10.1016/j.mehy.2008.10.032. PubMed DOI

KUMRAL A, YESILIRMAK DC, SONMEZ U, BASKIN H, TUGYAN K, YILMAZ O, GENC S, GOKMEN N, GENC K, DUMAN N, OZKAN H. Neuroprotective effect of the peptides ADNF-9 and NAP on hypoxic-ischemic brain injury in neonatal rats. Brain Res. 2006;1115:169–178. doi: 10.1016/j.brainres.2006.07.114. PubMed DOI

KUMRAL A, YESILIRMAK DC, SOZMEN S, ERGUR BU, TUGYAN K, OZBAL S, GUCLU S, DUMAN N, OZKAN H. Effect of leptin treatment on neonatal hypoxic-ischemic brain injury. J Matern Fetal Neonatal Med. 2012;25:141–146. doi: 10.3109/14767058.2011.565834. PubMed DOI

LAFUENTE H, PAZOS MR, ALVAREZ A, MOHAMMED N, SANTOS M, ARIZTI M, ALVAREZ FJ, MARTINEZ-ORGADO JA. Effects of cannabidiol and hypothermia on short-term brain damage in new-born piglets after acute hypoxia-ischemia. Front Neurosci. 2016;10:323. doi: 10.3389/fnins.2016.00323. PubMed DOI PMC

LAPTOOK AR, SHANKARAN S, TYSON JE, MUNOZ B, BELL EF, GOLDBERG RN, PARIKH NA, AMBALAVANAN N, PEDROZA C, PAPPAS A. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial. JAMA. 2017;318:1550–1560. doi: 10.1001/jama.2017.14972. PubMed DOI PMC

LAW LS-C, LO EA-G, CHAN CC-C, GAN TJ. Neurologic and cognitive outcomes associated with the clinical use of xenon: a systematic review and meta-analysis of randomized-controlled trials. Can J Anesth. 2018;65:1041–1056. doi: 10.1007/s12630-018-1163-6. PubMed DOI

LAWN JE, COUSENS S, ZUPAN J, TEAM LNSS. 4 million neonatal deaths: when? Where? Why? Lancet. 2005;365:891–900. doi: 10.1016/S0140-6736(05)71048-5. PubMed DOI

LEE ACC, KOZUKI N, BLENCOWE H, VOS T, BAHALIM A, DARMSTADT GL, NIERMEYER S, ELLIS M, ROBERTSON NJ, COUSENS S, LAWN JE. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74:50–72. doi: 10.1038/pr.2013.206. PubMed DOI PMC

LEKER RR, TEICHNER A, GRIGORIADIS N, OVADIA H, BRENNEMAN DE, FRIDKIN M, GILADI E, ROMANO J, GOZES I. NAP, a femtomolar-acting peptide, protects the brain against ischemic injury by reducing apoptotic death. Stroke. 2002;33:1085–1092. doi: 10.1161/01.STR.0000014207.05597.D7. PubMed DOI

LEVITON A, NELSON KB. Problems with definitions and classifications of newborn encephalopathy. Pediatr Neurol. 1992;8:85–90. doi: 10.1016/0887-8994(92)90026-U. PubMed DOI

LI C, MO Z, LEI J, LI H, FU R, HUANG Y, LUO S, ZHANG L. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway. Int J Biochem Cell Biol. 2018;99:169–177. doi: 10.1016/j.biocel.2018.03.020. PubMed DOI

LI W, YANG J, ZHOU D, ZHANG J, ZHUO Q. Meta-analysis evaluation of the treatment of neonatal hypoxic-ischemic encephalopathy with ganglioside. Biocell. 2019;43:7. doi: 10.32604/biocell.2019.04763. DOI

LI Y-X, DING S-J, XIAO L, GUO W, ZHAN Q. Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1α and erythropoietin. Neurosci Bull. 2008;24:89–95. doi: 10.1007/s12264-008-0089-3. PubMed DOI PMC

LINGAM I, ROBERTSON NJ. Magnesium as a neuroprotective agent: a review of its use in the fetus, term infant with neonatal encephalopathy, and the adult stroke patient. Dev Neurosci. 2018;40:1–12. doi: 10.1159/000484891. PubMed DOI

LIU Y, BARKS JD, XU G, SILVERSTEIN FS. Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats. Stroke. 2004;35:1460–1465. doi: 10.1161/01.STR.0000128029.50221.fa. PubMed DOI

LUCKI NC, SEWER MB. Nuclear sphingolipid metabolism. Ann Rev Physiol. 2012;74:131–151. doi: 10.1146/annurev-physiol-020911-153321. PubMed DOI PMC

LUND SA, GIACHELLI CM, SCATENA M. The role of osteopontin in inflammatory processes. J Cell Commun Signal. 2009;3:311–322. doi: 10.1007/s12079-009-0068-0. PubMed DOI PMC

MAIWALD CA, ANNINK KV, RÜDIGER M, BENDERS MJ, Van BEL F, ALLEGAERT K, NAULAERS G, BASSLER D, KLEBERMAß-SCHREHOF K, VENTO M. Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III) BMC Pediatr. 2019;19:210. doi: 10.1186/s12887-019-1566-8. PubMed DOI PMC

MAREŠ J, POMETLOVÁ M, DEYKUN K, KRÝSL D, ROKYTA R. An isolated epileptic seizure elicits learning impairment which could be prevented by melatonin. Epilepsy Behav. 2012;23:199–204. doi: 10.1016/j.yebeh.2011.11.018. PubMed DOI

MARESOVA D, RILJAK V, MARES J. Melatonin modulates hypoxia-induced changes of rat brain excitability. Gen Physiol Biophys. 2010;29:67–71. doi: 10.4149/gpb_2010_01_71. PubMed DOI

MARKOWITZ CE. Interferon-beta: mechanism of action and dosing issues. Neurology. 2007;68(24 Suppl 4):S8–S11. doi: 10.1212/01.wnl.0000277703.74115.d2. PubMed DOI

MARTINEZ-BIARGE M, DIEZ-SEBASTIAN J, WUSTHOFF CJ, MERCURI E, COWAN FM. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics. 2013;132:e952–e959. doi: 10.1542/peds.2013-0511. PubMed DOI

MARTÍNEZ-ORGADO J, FERNÁNDEZ-FRUTOS B, GONZÁLEZ R, ROMERO E, URIGÜEN L, ROMERO J, VIVEROS MP. Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia. Brain Res Mol Brain Res. 2003;114:132–139. doi: 10.1016/S0169-328X(03)00163-3. PubMed DOI

MATĚJOVSKÁ I, BERNÁŠKOVÁ K, KRÝSL D, MAREŠ J. Influence of melatonin pretreatment and preconditioning by hypobaric hypoxia on the development of cortical photothrombotic ischemic lesion. Physiol Res. 2008;57:283–288. PubMed

MILLAR LJ, SHI L, HOERDER-SUABEDISSEN A, MOLNÁR Z. Neonatal hypoxia ischaemia: mechanisms, models, and therapeutic challenges. Front Cell Neurosci. 2017;11 doi: 10.3389/fncel.2017.00078. PubMed DOI PMC

MOHAMMED N, CEPRIAN M, JIMENEZ L, RUTH PAZOS M, MARTÍNEZ-ORGADO J. Neuroprotective effects of cannabidiol in hypoxic ischemic insult. The therapeutic window in newborn mice. CNS Neurol Disord Drug Targets. 2017;16:102–108. doi: 10.2174/1871527315666160927110305. PubMed DOI

MURDEN S, BORBÉLYOVÁ V, LAŠTŮVKA Z, MYSLIVEČEK J, OTÁHAL J, RILJAK V. Gender differences involved in the pathophysiology of the perinatal hypoxic-ischemic damage. Physiol Res. 2019;68(Suppl 3):S207–S217. doi: 10.33549/physiolres.934356. PubMed DOI

NAGAYAMA T, SINOR AD, SIMON RP, CHEN J, GRAHAM SH, JIN K, GREENBERG DA. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci. 1999;19:2987–2995. doi: 10.1523/JNEUROSCI.19-08-02987.1999. PubMed DOI PMC

NAIR J, KUMAR VH. Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Children. 2018;5:99. doi: 10.3390/children5070099. PubMed DOI PMC

NIE X, LOWE DW, ROLLINS LG, BENTZLEY J, FRASER JL, MARTIN R, SINGH I, JENKINS D. Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia. Neurosci Res. 2016;108:24–33. doi: 10.1016/j.neures.2016.01.008. PubMed DOI PMC

NITKIN CR, RAJASINGH J, PISANO C, BESNER GE, THÉBAUD B, SAMPATH V. Stem cell therapy for preventing neonatal diseases in the 21st century: Current understanding and challenges. Pediatr Res. 2020;87:265–276. doi: 10.1038/s41390-019-0425-5. PubMed DOI PMC

NOH M-R, KIM SK, SUN W, PARK SK, CHOI HC, LIM JH, KIM IH, KIM H-J, KIM H, EUN B-L. Neuroprotective effect of topiramate on hypoxic ischemic brain injury in neonatal rats. Exp Neurol. 2006;201:470–478. doi: 10.1016/j.expneurol.2006.04.038. PubMed DOI

NOOR JI, IKEDA T, MISHIMA K, AOO N, OHTA S, EGASHIRA N, IWASAKI K, FUJIWARA M, IKENOUE T. Short-term administration of a new free radical scavenger, edaravone, is more effective than its long-term administration for the treatment of neonatal hypoxic-ischemic encephalopathy. Stroke. 2005;36:2468–2474. doi: 10.1161/01.STR.0000185653.49740.c6. PubMed DOI

NOOR JI, UEDA Y, IKEDA T, IKENOUE T. Edaravone inhibits lipid peroxidation in neonatal hypoxic-ischemic rats: an in vivo microdialysis study. Neurosci Lett. 2007;414:5–9. doi: 10.1016/j.neulet.2006.10.024. PubMed DOI

PACELLA MJ, DOUGLAS-ESCOBAR M, ZHENG T, WEISS MD. Frontiers in Stem Cell and Regenerative Medicine Research. Vol. 3. Bentham Science Publishers; 2017. Stem cell therapy for brain injury in neonates; pp. 68–101. DOI

PALMANO K, ROWAN A, GUILLERMO R, GUAN J, McJARROW P. The role of gangliosides in neurodevelopment. Nutrients. 2015;7:3891–3913. doi: 10.3390/nu7053891. PubMed DOI PMC

PALMER C, ROBERTS RL, BERO C. Deferoxamine posttreatment reduces ischemic brain injury in neonatal rats. Stroke. 1994;25:1039–1045. doi: 10.1161/01.STR.25.5.1039. PubMed DOI

PAPPA KI, ANAGNOU NP. Novel sources of fetal stem cells: where do they fit on the developmental continuum? Regen Med. 2009;4:423–433. doi: 10.2217/rme.09.12. PubMed DOI

PAPROCKA J, KIJONKA M, RZEPKA B, SOKÓŁ M. Melatonin in hypoxic-ischemic brain injury in term and preterm babies. Int J Endocrinol. 2019;2019:9626715. doi: 10.1155/2019/9626715. PubMed DOI PMC

PARIKH P, JUUL SE. Neuroprotective strategies in neonatal brain injury. J Pediatr. 2018;192:22–32. doi: 10.1016/j.jpeds.2017.08.031. PubMed DOI

PARNHAM MJ, HABER VE, GIAMARELLOS-BOURBOULIS EJ, PERLETTI G, VERLEDEN GM, VOS R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014;143:225–245. doi: 10.1016/j.pharmthera.2014.03.003. PubMed DOI

PAZOS M, CINQUINA V, GÓMEZ A, LAYUNTA R, SANTOS M, FERNÁNDEZ-RUIZ J, MARTÍNEZ-ORGADO J. Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function. Neuropharmacology. 2012;63:776–783. doi: 10.1016/j.neuropharm.2012.05.034. PubMed DOI

PEETERS-SCHOLTE C, BRAUN K, KOSTER J, KOPS N, BLOMGREN K, BUONOCORE G, Van BUUL-OFFERS S, HAGBERG H, NICOLAY K, Van BEL F. Effects of allopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal hypoxia-ischemia. Pediatr Res. 2003;54:516–522. doi: 10.1203/01.PDR.0000081297.53793.C6. PubMed DOI

PIN TW, ELDRIDGE B, GALEA MP. A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy. Eur J Paediatr Neurol. 2009;13:224–234. doi: 10.1016/j.ejpn.2008.05.001. PubMed DOI

PRENDERVILLE JA, KELLY ÁM, DOWNER EJ. The role of cannabinoids in adult neurogenesis. Br J Pharmacol. 2015;172:3950–3963. doi: 10.1111/bph.13186. PubMed DOI PMC

RAMIREZ MR, MURARO F, ZYLBERSZTEJN DS, ABEL CR, ARTENI NS, LAVINSKY D, NETTO CA, TRINDADE VM. Neonatal hypoxia-ischemia reduces ganglioside, phospholipid and cholesterol contents in the rat hippocampus. Neurosci Res. 2003;46:339–347. doi: 10.1016/S0168-0102(03)00100-7. 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

RILJAK V, LAŠTŮVKA Z, MYSLIVEČEK J, BORBÉLYOVÁ V, OTÁHAL J. Early postnatal hypoxia induces behavioral deficits but not morphological damage in the hippocampus in adolescent rats. Physiol Res. 2020;69:165–179. doi: 10.33549/physiolres.934234. PubMed DOI PMC

ROBERTSON CMT, FINER NN, GRACE MGA. School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term. J Pediatr. 1989;114:753–760. doi: 10.1016/S0022-3476(89)80132-5. PubMed DOI

ROBERTSON NJ, FAULKNER S, FLEISS B, BAINBRIDGE A, ANDORKA C, PRICE D, POWELL E, LECKY-THOMPSON L, THEI L, CHANDRASEKARAN M. Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model. Brain. 2013;136:90–105. doi: 10.1093/brain/aws285. PubMed DOI

RODRÍGUEZ-FANJUL J, FERNÁNDEZ-FEIJÓO CD, LOPEZ-ABAD M, RAMOS MGL, CABALLE RB, ALCÁNTARA-HORILLO S, CAMPRUBI MC. Neuroprotection with hypothermia and allopurinol in an animal model of hypoxic-ischemic injury: Is it a gender question? PLoS One. 2017;12:e0184643. doi: 10.1371/journal.pone.0184643. PubMed DOI PMC

SABIR H, OSREDKAR D, MAES E, WOOD T, THORESEN M. Xenon combined with therapeutic hypothermia is not neuroprotective after severe hypoxia-ischemia in neonatal rats. PLoS One. 2016;11:e0156759. doi: 10.1371/journal.pone.0156759. PubMed DOI PMC

SARNAT HB, SARNAT MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol. 1976;33:696–705. doi: 10.1001/archneur.1976.00500100030012. PubMed DOI

SATOH K, IKEDA Y, SHIODA S, TOBE T, YOSHIKAWA T. Edarabone scavenges nitric oxide. Redox Rep. 2002;7:219–222. doi: 10.1179/135100002125000587. PubMed DOI

SCHIAVON AP, SOARES LM, BONATO JM, MILANI H, GUIMARAES FS, De OLIVEIRA RMW. Protective effects of cannabidiol against hippocampal cell death and cognitive impairment induced by bilateral common carotid artery occlusion in mice. Neurotox Res. 2014;26:307–316. doi: 10.1007/s12640-014-9457-0. PubMed DOI

SCHUBERT S, BRANDL U, BRODHUN M, ULRICH C, SPALTMANN J, FIEDLER N, BAUER R. Neuroprotective effects of topiramate after hypoxia-ischemia in newborn piglets. Brain Res. 2005;1058:129–136. doi: 10.1016/j.brainres.2005.07.061. PubMed DOI

SCHUBRING C, KIESS W, ENGLARO P, RASCHER W, DOTSCH J, HANITSCH S, ATTANASIO A, BLUM W. Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight. J Clin Endocrinol Metab. 1997;82:1480–1483. doi: 10.1210/jcem.82.5.3935. PubMed DOI

SHAH PS. Hypothermia: a systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med. 2010;15:238–246. doi: 10.1016/j.siny.2010.02.003. PubMed DOI

SHANKARAN S, LAPTOOK AR, EHRENKRANZ RA, TYSON JE, McDONALD SA, DONOVAN EF, FANAROFF AA, POOLE WK, WRIGHT LL, HIGGINS RD. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–1584. doi: 10.1056/NEJMcps050929. PubMed DOI

SHENG L, LI Z. Adjuvant treatment with monosialoganglioside may improve neurological outcomes in neonatal hypoxic-ischemic encephalopathy: A meta-analysis of randomized controlled trials. PLoS One. 2017;12 doi: 10.1371/journal.pone.0183490. PubMed DOI PMC

SHIBUTA S, VARATHAN S, KAMIBAYASHI T, MASHIMO T. Small temperature variations alter edaravone-induced neuroprotection of cortical cultures exposed to prolonged hypoxic episodes. Br J Anaesth. 2010;104:52–58. doi: 10.1093/bja/aep320. PubMed DOI

SMITH-SWINTOSKY VL, GOZES I, BRENNEMAN DE, D’ANDREA MR, PLATA-SALAMAN CR. Activity-dependent neurotrophic factor-9 and NAP promote neurite outgrowth in rat hippocampal and cortical cultures. J Mol Neurosci. 2005;25:225–238. doi: 10.1385/JMN:25:3:225. PubMed DOI

SO H-Y. Therapeutic hypothermia. Korean J Anesthesiol. 2010;59:299–304. doi: 10.4097/kjae.2010.59.5.299. PubMed DOI PMC

SOKOLOWSKA P, PASSEMARD S, MOK A, SCHWENDIMANN L, GOZES I, GRESSENS P. Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy. Neuroscience. 2011;173:156–168. doi: 10.1016/j.neuroscience.2010.10.074. PubMed DOI

SUGANUMA H, ARAI Y, KITAMURA Y, HAYASHI M, OKUMURA A, SHIMIZU T. Maternal docosahexaenoic acid-enriched diet prevents neonatal brain injury. Neuropathology. 2010;30:597–605. doi: 10.1111/j.1440-1789.2010.01114.x. PubMed DOI

SUGAWA M, SAKURAI Y, ISHIKAWA-IEDA Y, SUZUKI H, ASOU H. Effects of erythropoietin on glial cell development; oligodendrocyte maturation and astrocyte proliferation. Neurosci Res. 2002;44:391–403. doi: 10.1016/S0168-0102(02)00161-X. PubMed DOI

SUGIMOTO J, ROMANI AM, VALENTIN-TORRES AM, LUCIANO AA, KITCHEN CMR, FUNDERBURG N, MESIANO S, BERNSTEIN HB. Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism. J Immunol. 2012;188:6338–6346. doi: 10.4049/jimmunol.1101765. PubMed DOI PMC

SUN J, WANG F, LI H, ZHANG H, JIN J, CHEN W, PANG M, YU J, HE Y, LIU J. Neuroprotective effect of sodium butyrate against cerebral ischemia/reperfusion injury in mice. Biomed Res Int. 2015;2015:412946. doi: 10.1155/2015/395895. PubMed DOI PMC

TAGIN MA, WOOLCOTT CG, VINCER MJ, WHYTE RK, STINSON DA. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012;166:558–566. doi: 10.1001/archpediatrics.2011.1772. PubMed DOI

TAKIZAWA Y, MIYAZAWA T, NONOYAMA S, GOTO Y-I, ITOH M. Edaravone inhibits DNA peroxidation and neuronal cell death in neonatal hypoxic-ischemic encephalopathy model rat. Pediatr Res. 2009;65:636–641. doi: 10.1203/PDR.0b013e3181a16a9f. PubMed DOI

TANAKA M. Pharmacological and clinical profile of the free radical scavenger edaravone as a neuroprotective agent. (Article in Japanese) Nihon Yakurigaku Zasshi. 2002;119:301–308. doi: 10.1254/fpj.119.301. PubMed DOI

TITOMANLIO L, KAVELAARS A, DALOUS J, MANI S, EL GHOUZZI V, HEIJNEN C, BAUD O, GRESSENS P. Stem cell therapy for neonatal brain injury: perspectives and challenges. Ann Neurol. 2011;70:698–712. doi: 10.1002/ana.22518. PubMed DOI

TOADER A-M, FILIP A, DECEA N, MURESAN A. Neuroprotective strategy in an experimental newborn rat model of brain ischemia and hypoxia: effects of resveratrol and hypothermia. Clujul Med. 2013;86:203–207. PubMed PMC

TOLAYMAT Y, DORÉ S, GRIFFIN HW, SHIH S, EDWARDS ME, WEISS MD. Inhaled gases for neuroprotection of neonates: a review. Front Pediatr. 2020;7:558. doi: 10.3389/fped.2019.00558. PubMed DOI PMC

TREVISANI VFM, CASTRO AA, NETO JFN, ATALLAH ÁN. Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database Syst Rev. 2013;2013:CD002265. doi: 10.1002/14651858.CD002265.pub3. PubMed DOI PMC

Van BEL F, GROENENDAAL F. Birth asphyxia-induced brain damage: the long road to optimal reduction and prevention! Pediat Med. 2020;3 doi: 10.21037/pm.2019.11.02. DOI

Van der KOOIJ MA, GROENENDAAL F, KAVELAARS A, HEIJNEN CJ, Van BEL F. Neuroprotective properties and mechanisms of erythropoietin in in vitro and in vivo experimental models for hypoxia/ischemia. Brain Res Rev. 2008;59:22–33. doi: 10.1016/j.brainresrev.2008.04.007. PubMed DOI

Van VELTHOVEN CTJ, HEIJNEN CJ, Van BEL F, KAVELAARS A. Osteopontin enhances endogenous repair after neonatal hypoxic-ischemic brain injury. Stroke. 2011;42:2294–2301. doi: 10.1161/STROKEAHA.110.608315. PubMed DOI

Van VELTHOVEN CT, KAVELAARS A, Van BEL F, HEIJNEN CJ. Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function. J Neurosci. 2010;30:9603–9611. doi: 10.1523/JNEUROSCI.1835-10.2010. PubMed DOI PMC

VELDHUIS WB, DERKSEN JW, FLORIS S, Van der MEIDE PH, De VRIES HE, SCHEPERS J, VOS IM, DIJKSTRA CD, KAPPELLE LJ, NICOLAY K. Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat. J Cereb Blood Flow Metab. 2003;23:1029–1039. doi: 10.1097/01.WCB.0000080703.47016.B6. PubMed DOI

VILLAPOL S, FAU S, RENOLLEAU S, BIRAN V, CHARRIAUT-MARLANGUE C, BAUD O. Melatonin promotes myelination by decreasing white matter inflammation after neonatal stroke. Pediatr Res. 2011;69:51–55. doi: 10.1203/PDR.0b013e3181fcb40b. PubMed DOI

VOLPE JJ. Perinatal brain injury: from pathogenesis to neuroprotection. Ment Retard Dev Disabil Res Rev. 2001;7:56–64. doi: 10.1002/1098-2779(200102)7:1<56::AID-MRDD1008>3.0.CO;2-A. PubMed DOI

VOLPE JJ. Neonatal encephalopathy: An inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012;72:156–166. doi: 10.1002/ana.23647. PubMed DOI

WACHTEL EV, HENDRICKS-MUÑOZ KD. Current management of the infant who presents with neonatal encephalopathy. Curr Probl Pediatr Adolesc Health Care. 2011;41:132–153. doi: 10.1016/j.cppeds.2010.12.002. PubMed DOI

WANG Q, LV H, LU L, REN P, LI L. Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury. J Matern Fetal Neonatal Med. 2019;32:3685–3692. doi: 10.1080/14767058.2018.1468881. PubMed DOI

WASSINK G, DAVIDSON JO, DHILLON SK, ZHOU K, BENNET L, THORESEN M, GUNN AJ. Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy. Curr Neurol Neurosci Rep. 2019;19:2. doi: 10.1007/s11910-019-0916-0. PubMed DOI

WEISS S, REYNOLDS BA, VESCOVI AL, MORSHEAD C, CRAIG CG, Van der KOOY D. Is there a neural stem cell in the mammalian forebrain? Trends Neurosci. 1996;19:387–393. doi: 10.1016/S0166-2236(96)10035-7. PubMed DOI

WEST T, ATZEVA M, HOLTZMAN DM. Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury. Dev Neurosci. 2007;29:363–372. doi: 10.1159/000105477. PubMed DOI PMC

WOOD T, OSREDKAR D, PUCHADES M, MAES E, FALCK M, FLATEBØ T, WALLØE L, SABIR H, THORESEN M. Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia. Sci Rep. 2016;6:23430. doi: 10.1038/srep23430. PubMed DOI PMC

WU YW, BAUER LA, BALLARD RA, FERRIERO DM, GLIDDEN DV, MAYOCK DE, CHANG T, DURAND DJ, SONG D, BONIFACIO SL. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics. 2012;130:683–691. doi: 10.1542/peds.2012-0498. PubMed DOI PMC

WU YW, GONZALEZ FF. Erythropoietin: a novel therapy for hypoxic-ischaemic encephalopathy? Dev Med Child Neurol. 2015;57(Suppl 3):34–39. doi: 10.1111/dmcn.12730. PubMed DOI

YAMAMOTO Y, KUWAHARA T, WATANABE K, WATANABE K. Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. Redox Rep. 1996;2:333–338. doi: 10.1080/13510002.1996.11747069. PubMed DOI

YAMATO S, NAKAMURA S, HTUN Y, NAKAMURA M, JINNAI W, NAKAO Y, MITSUIE T, KOYANO K, WAKABAYASHI T, MORIMOTO AH. Intravenous edaravone plus therapeutic hypothermia offers limited neuroprotection in the hypoxic-ischaemic newborn piglet. Neonatology. 2020;2020:1–8. doi: 10.1101/2020.02.25.964288. PubMed DOI

YASUOKA N, NAKAJIMA W, ISHIDA A, TAKADA G. Neuroprotection of edaravone on hypoxic-ischemic brain injury in neonatal rats. Brain Res Dev Brain Res. 2004;151:129–139. doi: 10.1016/j.devbrainres.2004.04.006. PubMed DOI

YOUSUF S, ATIF F, AHMAD M, HODA N, ISHRAT T, KHAN B, ISLAM F. Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. Brain Res. 2009;1250:242–253. doi: 10.1016/j.brainres.2008.10.068. PubMed DOI

YU J, VODYANIK MA, SMUGA-OTTO K, ANTOSIEWICZ-BOURGET J, FRANE JL, TIAN S, NIE J, JONSDOTTIR GA, RUOTTI V, STEWART R. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–1920. doi: 10.1126/science.1151526. PubMed DOI

ZHANG F, WANG S, SIGNORE AP, CHEN J. Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia. Stroke. 2007;38:2329–2336. doi: 10.1161/STROKEAHA.107.482786. PubMed DOI

ZHANG W, HU X, YANG W, GAO Y, CHEN J. Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions. Stroke. 2010;41:2341–2347. doi: 10.1161/STROKEAHA.110.586081. PubMed DOI PMC

ZHOU Y, YAO Y, SHENG L, ZHANG J, ZHANG JH, SHAO A. Osteopontin as a candidate of therapeutic application for the acute brain injury. J Cell Mol Med. 2020;24:8918–8929. doi: 10.1111/jcmm.15641. PubMed DOI PMC

ZIEMKA-NALECZ M, JAWORSKA J, SYPECKA J, POLOWY R, FILIPKOWSKI RK, ZALEWSKA T. Sodium butyrate, a histone deacetylase inhibitor, exhibits neuroprotective/neurogenic effects in a rat model of neonatal hypoxia-ischemia. Mol Neurobiol. 2017;54:5300–5318. doi: 10.1007/s12035-016-0049-2. PubMed DOI PMC

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