Abstract
Hypoxic-ischemic encephalopathy (HIE), the most common cause of neurologic disease during the perinatal period, is associated with a high mortality and morbidity rate and also has long-term consequences like cerebral palsy, mental retardation, and seizures. Perinatal HIE is caused by processes that alter the cerebral blood flow (CBF) in the fetus and newborn compromising the supply of oxygen to the brain. They may develop antepartum (20%), intrapartum (30%), antepartum and intrapartum (35%), or postpartum (10%). Acute or long-term consequences of HIE are related either to necrosis or to apoptosis of neuronal cells. Cell necrosis will lead to generalized disruption of internal homeostasis and eventually to the lysis of the cells, which give rise to an inflammatory response with the release of oxygen free radicals and activation of the microglial cells. Apoptosis is programmed cell death, not associated with the lysis of the plasma membrane and inflammation, which can be triggered by hypoxia. It is crucial to restore any failures in the respiratory and circulatory systems, in order to prevent neuronal cell death. However, neonatologists should also be aware of the hazards of medically induced hyperoxia (high FIO2) because this condition may increase the production of oxygen free radicals thus worsening the neuronal insult. Elucidating basic cellular mechanisms in response to hypoxia of the developing brain will enable the development of novel strategies for preventing or attenuating the deleterious effects of hypoxia in the human newborn.
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References
Aizenman E, Lipton SA, Loring RH (1989) Selective modulation of NMDA responses by reduction and oxidation. Neuron 2:1257–1263
Angeles DM, Wycliffe N, Michelson D et al (2005) Use of opioids in asphyxiated term neonates: effects of neuroimaging and clinical outcome. Pediatr Res 57:873–878
Angeles DM, Ashwal S, Wycliffe ND et al (2007) Relationship between opioid therapy, tissue damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates. Pediatr Res 60:614–621
Aoki C, Fenstemaker S, Lubin M et al (1993) Nitric oxide synthase in the visual cortex of monocular monkeys as revealed by light and electron microscopic immunocytochemistry. Brain Res 620:97–113
Aoki C, Rhee J, Lubin M et al (1997) NMDA-R1 subunit of the cerebral cortex co-localizes with neuronal nitric oxide synthase at pre and postsynaptic sites and in spines. Brain Res 750:25–140
Ashraf QM, Mishra OP, Delivoria-Papadopoulos M (2007) Mechanisms of expression of apoptotic protease activating factor-1 (Apaf-1) in nuclear, mitochondrial and cytosolic fractions of the cerebral cortex of newborn piglets. Neurosci Lett 415:253–258
Azzopardi D, Robertson NJ, Cowan FM et al (2000) Pilot study of treatment with whole body hypothermia for neonatal encephalopathy. Pediatrics 106:684–694
Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O et al (2014) Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med 371:140–149. https://doi.org/10.1056/NEJMoa1315788
Bashir ZI, Alford S, Davies SN et al (1991) Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature 349:156–158
Battin MR, Dezoete JA, Gunn TR et al (2001) Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia. Pediatrics 107:480–484
Battin MR, Penrice J, Gunn TR, Gunn AJ (2003) Treatment of term infants with head cooling and systematic hypothermia (35.0 degrees and 34.5 degrees C) after perinatal asphyxia. Pediatrics 111:244–251
Baum RM (1984) Superoxide theory of oxygen toxicity is center of heated debate. Chem Eng News 9:20–28
Beckman JS (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87:1620–1624
Beckman JS (1991) The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J Dev Physiol 15:53–59
Bender MJ, Bos AF, Rademaker CM et al (2006) Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia. Arch Dis Child Fetal Neonatal Ed 91:F163–F165
Benichou J, Zupan V, Fernandez H et al (1997) Tocolytic magnesium sulphate and pediatric mortality. Lancet 351:290–291
Bhat GK, Mahesh VB, Lamar CA et al (1997) Histochemical localization of nitric oxide neurons in the hypothalamus: association with gonadotropin-releasing hormone neurons and co-localization with N-methyl-D-aspartate receptors. Neuroendocrinol Lett 62:187–197
Bredt DS, Ferris CD, Snyder SH (1992) Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase, identification of flavin and calmodulin sites. J Biol Chem 267:10976–10981
Cazevielle C (1993) Superoxide and nitric oxide cooperation in hypoxia/reoxygenation-induced neuron injury. Free Radic Biol Med 14:359–395
Chaudhari T, McGuire W (2008) Allopurinol for preventing mortality and morbidity in newborn infants with suspected hypoxic-ischemic encephalopathy. Cochrane Database Syst Rev 2:CD006817
Chawla S, Bading H (2001) CREB/CBP and SRE-interacting transcriptional regulators are fast on-off switches: duration of calcium transients specifies the magnitude of transcriptional responses. J Neurochem 79:849–858
Chein S, Oeltgen PR, Diana JN et al (1994) Extension of tissue survival time in multiorgan block preparation with a delta DADLE (D-Ala2, D-leu5)-enkephalin). J Thorac Cardiovasc Surg 107:964–967
Chen J, Zhu RL, Nakayama M et al (1996) Expression of the apoptosis- effector gene, Bax, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia. J Neurochem 67:64–71
Chiang MC, Ashraf QM, Ara J et al (2007) Mechanism of caspase-3 activation during hypoxia in the cerebral cortex of newborn piglets. Neurosci Lett 421:67–71
Chiang MC, Ashraf QM, Mishra OP, Delivoria-Papadopoulos M (2008) Mechanism of DNA fragmentation during hypoxia in the cerebral cortex of newborn piglets. Neurochem Res 33:1232–1237
Choi DW (1990) Cerebral hypoxia: some new approaches and unanswered questions. J Neurosci 10:2493–2501
Christopherson KS, Hillier BJ, Lim WAS et al (1999) PSD-95 assembles a ternary complex with the N-Methyl-D-Aspartic acid receptor and bivalent neuronal NO synthase PDX domain. J Boi Chem 274:27467–27473
Clancy RR, McGaurn SA, Goin JE et al (2001) Allopurinol neurocardiac protection trial in infants undergoing heart surgery using deep hypothermic circulatory arrest. Pediatrics 108:61–70
Coimbria C, Wielock T (1994) Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia. Acta Neuropathol (Berlin) 87:325–331
Collingridge G (1987) Synaptic plasticity. The role of NMDA receptors in learning and memory. Nature 330:604–605
Columbano A (1995) Cell death: current difficulties in discriminating apoptosis and necrosis in the context of pathological processes in vivo. J Cell Biochem 58:181–190
Davidson JO, Wassink G, van den Heuij LG et al (2015) Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy – where to from here? Front Neurol 14:6–198
Dawson VL (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci U S A 88:6368–6371
Dawson DA (1994a) Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome. Cerebrovasc Brain Metab 64:299–324
Dawson TM (1994b) Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J Neurosci 14:5147–5159
Dawson TM, Steiner JP, Dawson VL et al (1993) Immunosuppressant FK506 enhances phosphorylation of nitric oxide synthase and protects against glutamate neurotoxicity. Proc Natl Acad Sci U S A 90:9808–9812
Debillon T, Daoud P, Durand P et al (2003) Whole-body cooling after perinatal asphyxia: a study in term neonates. Dev Med Child Neurol 45:17–23
Delivoria-Papadopoulos M, Mishra OP (1998) Mechanisms of cerebral injury in perinatal asphyxia and strategies for prevention. J Pediatr 132:S30–S34
Delivoria-Papadopoulos M, Akhter W, Mishra OP (2003) Hypoxia-induced Ca2+ -influx in cerebral cortical neuronal nuclei of newborn piglets. Neurosci Lett 342:119–123
Delivoria-Papadopoulos M, Ashraf QM, Ara J, Mishra OP (2008) Nuclear mechanisms of hypoxic cerebral injury in the newborn: the role of caspases. Semin Perinatol 32:334–343
Delivoria-Papadopoulos M, Ashraf QM, Mishra OP (2001a) Brain tissue energy dependence of CaM kinase IV cascade activation during hypoxia in the cerebral cortex of newborn piglets. Neurosci Lett 491(2):113–117
Delivoria-Papadopoulos M, Ashraf QM, Mishra OP (2001b) Mechanism of CaM kinase IV activation during hypoxia in neuronal nuclei of the cerebral cortex of newborn piglets: the role of Src kinase. Neurochem Res 36(8):1512–1519
Dolmetsch RE, Lewis RS, Goodnow CC (1997) Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386:855–858
Dolmetsch RE, Pajvani U, Fife K et al (2001) Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway. Science 294:333–339
Doyle LW, Crowther CA, Middleton P et al (2009) Magnesium bias sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 1:CD004661
Dragunow M, Beiharz E, Sirimanne E et al (1994) Immediately early gene protein expression in neurons undergoing delayed death, but not necrosis following hypoxic-ischemic injury to the young rat brain. Brain Res Mol Brain Res 25:1933
Eicher DJ, Wagner CL, Katikaneni LP et al (2005) Moderate hypothermia in neonatal encephalopathy: safety outcomes. Pediatr Neurol 32:18–24
Faraci FM (1991) Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. Am J Physiol 261:H1038–H1042
Ferrer I, Tortosa A, Macaya A et al (1994) Evidence of nuclear DNA fragmentation following hypoxia-ischemia in the infant rat brain, and transient forebrain ischemia in the adult gerbil. Brain Pathol 4:115–122
Fields RD, Esthete F, Stevens B et al (1997) Action potential-dependent regulation of gene expression: temporal specificity in Ca2+, cAMP-responsive element binding proteins, and mitogen-activated protein kinase signaling. J Neurosci 17:7252–7266
Fritz K, Delivoria-Papadopoulos M (2006) Mechanisms of injury to the newborn brain. Clin Perinatol 33:573–591
Fritz KI, Groenenedaal F, McGowan JE et al (1996) Effects of 3- (2-carboxy-piperzine-4-yl) propyl-1-phosphonic acid (CPP) on NMDA receptor binding characteristics and brain cell membrane function during cerebral hypoxia in newborn piglets. Brain Res 729:66–74
Ghosh A, Greenberg ME (1995) Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science 268:239–247
Gillardon F, Lenz C, Waschle KF (1996) Altered expression of Bcl- 2, Bcl-X, Bax and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats. Brain Res Mol Brain Res 40:254–260
Gluckman PD, Wyatt JS, Azzopardi D et al (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicenter randomized trial. Lancet 365:663–670
Gow AJ, Duran D, Malcom S et al (1996) Effect of peroxynitrite-induced protein modification on tyrosine phosphorylation and degradation. FEBS Lett 385:63–66
Gunn AJ, Gunn TR (1998) The ‘pharmacology’ of neuronal rescue with cerebral hypothermia. Early Hum Dev 53:19–35
Gunn AJ, Gluckman PD, Gunn TR (1998) Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 102:885–892
Gunn AJ, Bennet L, Gunning MI et al (1999) Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep. Pediatr Res 46:274–280
Gunn AJ, Battin M, Gluckman PD et al (2005) Therapeutic hypothermia: from lab to NICU. J Perinat Med 33:340–346
Hamada Y (1994) Inhibitors of nitric oxide synthesis reduce hypoxic-ischemic brain damage in the neonatal rat. Pediatr Res 35:10–14
Hameed A, Olsen KJ, Lee MK et al (1989) Cytolysis by Ca-permeable transmembrane channels: pore formation causes extensive DNA degradation and cell lysis. J Exp Med 169:765–777
Hardingham GE, Bading H (1998) Nuclear calcium: a key regulator of gene expression. Biometals 11:345–358
Hardingham GE, Chawla S, Cruzalegui FH, Bading H (1999) Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels. Neuron 22:789–798
Higgins RD, Rahu TN, Perlman J et al (2006) Hypothermia and perinatal asphyxia: executive summary of the national institute of child health and human development workshop. J Pediatr 148:170–175
Hill A, Volpe J (1999) Hypoxic-ischemic cerebral injury in the newborn. In: Swaiman KF, Ashwal S (eds) Pediatric neurology, principles and practice. Mosby, St. Louis, pp 191–204
Hoeger H, Engidawork E, Stolzlechner D et al (2006) Long-term effect of moderate and profound hypothermia on morphology, neurological, cognitive and behavioural functions in a rat model of perinatal asphyxia. Amino Acids 31:385–396
Hoffman DJ, Marro PJ, McGowan JE et al (1994a) Protective effect of MgSO4 infusion on NMDA receptor binding characteristics during cerebral cortical hypoxia in newborn piglets. Brain Res 644:144–149
Hoffman DJ, McGowan JE, Marro PJ et al (1994b) Hypoxia-induced modification of the N-methyl-D-aspartate (NMDA) receptor in the brain of newborn piglets. Neurosci Lett 167:156–160
Huang Z (1994) Effects of cerebral ischemia in mice deficient neuronal nitric oxide. Science 265:1883–1885
Ishida R, Akiyoshi H, Takahashi T (1974) Isolation and purification of calcium and magnesium dependent endonuclease from rat liver nuclei. Biochem Biophys Res Commun 56:703–710
Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG (2013) Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 1:CD003311.10.1002/14651858.CD003311.pub3
Johnston MV (1995) Neurotransmitters and vulnerability of the developing brain. Brain Dev 17:301–306
Kapetanakis A, Azzopardi D, Wyatt J et al (2008) Therapeutic hypothermia for neonatal encephalopathy: a UK survey of opinion, practice and neuron-investigation at the end of 2007. Acta Paediatr 98:631–635
Kiedrowski I, Costa E, Wroblewski JT (1992) Glutamate receptor agonist stimulate nitric oxide synthase in primary cultures of cerebellar granule cells. J Neuroch 58:335–341
Kitada S, Krajewski S, Miyashita T (1996) Gamma-radiation induces upregulation of Bax protein and apoptosis in radiosensitive cells in vivo. Oncogene 12:187–192
Kratimenos P, Koutroulis I, Marconi D et al (2014) Multi-targeted molecular therapeutic approach in aggressive neuroblastoma: the effect of Focal Adhesion Kinase–Src–Paxillin system. Expert Opin Ther Targets 18(12):1395–1406
Kratimenos P, Koutroulis I, Agarwal B, Theocharis S, Delivoria-Papadopoulos M (2017) Effect of concurrent Src kinase inhibition with short-duration hypothermia on Ca2+/calmodulin kinase IV activity and neuropathology after hypoxia-ischemia in the newborn swine brain. Sci Rep 7(1):16664. https://doi.org/10.1038/s41598-017-16983-1
Kratimenos P, Koutroulis I, Jain A, Malaeb S, Delivoria-Papadopoulos M (2018) Effect of Src kinase inhibition on cytochrome c, Smac/DIABLO and apoptosis inducing factor (AIF) following cerebral hypoxia-ischemia in newborn piglets. Neonatology 113(1):37–43. https://doi.org/10.1159/000480067
Kurinczuk JJ, White-Koning M, Badawi N (2010) Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 86(6):329–338
Lawn JE, Cousens S, Zupan J (2005) 4 million neonatal deaths: when? Where? Why? Lancet 365(9462):891–900
Lee J, Kim MS, Park C et al (2004) Morphine prevents glutamate-induced death of primary rat neonatal astrocytes through modulation of intracellular redox. Immunopharmacol Immunotoxicol 26:17–28
Legido A (1994) Perinatal hypoxic-ischemic encephalopathy: current advances in diagnosis and treatment. Int Pediatr 9:114–136
Legido A, Katsetos CD, Mishra OP et al (2001) Perinatal hypoxia-ischemia encephalopathy: current and future treatments. Int Pediatr 15:143–151
Lerea L, McNamara JO (1993) Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways. Neuron 10:31–41
Levene MI, Evans DJ, Mason S et al (1999) An international network for evaluation neuroprotective therapy after severe birth asphyxia. Sem Perinatol 23:226–233
Lim YJ, Zheng S, Zuo Z (2004) Morphine preconditions Purkinje cells against cell death under in vitro simulated ischemia- reperfusion conditions. Anesthesiology 100:562–568
Linnik MD, Zobirst RH, Hatfield MD (1993) Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Strokes 24:2002–2008
Lipton S (1999) Redox sensitivity of NMDA receptor. Meth Mol Biol 128:121–130
Maro PJ, Hoffman D, Schneiderman R et al (1998) Effect of allopurinol on NMDA receptor modification following recurrent asphyxia in newborn piglets. Brain Res 787:71–77
Marro PJ, McGowan JE, Razdan B et al (1994) Effect of allopurinol on uric acid levels and brain cell membrane Na+, K+-ATPase activity during hypoxia in newborn piglets. Brain Res 650:9–15
Mayer ML, Westbrook GL, Guthrie PB (1984) Voltage-dependent block by Mg++ of NMDA responses in spinal cord neurons. Nature 309:261–263
Mayfield KP, D’Alecy LG (1992) Role of endogenous opioid peptides in the acute adaptation to hypoxia. Brain Res 582:226–231
Mayfield KP, D’Alecy LG (1994) Delta-1 opioid agonist acutely increases hypoxic tolerance. J Pharmacol Exp Ther 268:683–688
Miller JA (1971) New approaches to preventing brain damage during asphyxia. Am J Obstet Gynecol 110:125–132
Mishra OP, Delivoria-Papadopoulos M (1992) NMDA receptor modification of the fetal guinea pig brain during hypoxia. Neurochem Res 17:1211–1216
Mishra OP, Delivoria-Papadopoulos M (1999) Cellular mechanisms of hypoxic injury in the developing brain. Brain Res Bull 48:233–238
Mishra OP, Delivoria-Papadopoulos M (2000) Hypoxia-induced generation of nitric oxide free radicals in cerebral cortex of newborn guinea pigs. Neurochem Res 25:1559–1565
Mishra OP, Delivoria-Papadopoulos M (2001) Effect of graded hypoxia on high-affinity Ca2+-ATPase activity in cortical neuronal nuclei of newborn piglets. Neurochem Res 26:1335–1341
Mishra OP, Delivoria-Papadopoulos M (2002) Nitric oxide-mediated Ca++-influx in neuronal nuclei and cortical synaptosomes of normoxic and hypoxic newborn piglets. Neurosci Lett 318:93–97
Mishra OP, Delivoria-Papadopoulos M (2006) Effect of neuronal nitric oxide synthase inhibition on caspase-9 activity during hypoxia in the cerebral cortex of newborn piglets. Neurosci Lett 401:81–85
Mishra OP, Delivoria-Papadopoulos M (2010) Mechanism of tyrosine phosphorylation of procaspase-9 and Apaf-1 in cytosolic fractions of the cerebral cortex of newborn piglets during hypoxia. Neurosci Lett 480:35–39
Mishra OP, Fritz KI, Delivoria-Papadopoulos M (2001) NMDA receptor and neonatal hypoxic brain injury. Ment Retard Dev Disabil Res Rev 7:249–253
Mittendorf R, Covert R, Boman J et al (1997) Is tocolytic magnesium sulphate associated with increased total pediatric mortality? Lancet 350:1517–1519
Monaghan DT, Olvenman HJ, Nguyen L et al (1988) Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine. Proc Natl Acad Sci U S A 85:9836–9840
Monaghan DT, Bridges RJ, Cotman CW (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol 29:365–402
Moriette G, Barrat J, Truffert P et al (2008) Effect of magnesium sulphate on mortality and neurologic morbidity of the very preterm newborn (of less than 33 weeks) with two-year neurological outcome: results of the prospective PREMAG trial. Gynecol Obstet Fertil 36:278–288
Nelson KB, Grether JK (1995) Can magnesium sulphate reduce the risk of cerebral palsy in very low birth weight infants? Pediatrics 95:263–269
Nowak L, Bregetovski P, Ascher P et al (1984) Magnesium gates glutamate-activated channels in mouse central neurons. Nature 307:462–465
Nowicki JP (1991) Nitric oxide mediates neuronal death after focal cerebral ischemia in the mouse. Eur J Pharmacol 204:339–340
Numagami Y (1997) Lipid free radical generation and brain cell membrane alteration following nitric oxide synthase inhibition during cerebral hypoxia in the newborn piglet. J Neurochem 69:1542–1547
Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619
Palmer C, Roberts RL (1991) Reduction of perinatal brain damage with oxypurinol treatment after hypoxic-ischemic injury. Pediatr Res 29:362–368
Palmer C, Vanucci RC, Towfighi J (1990) Reduction of perinatal hypoxic-ischemic brain damage with allopurinol. Res Pediatr 27:332–336
Parikh NA, Lasky RE, Garza CN et al (2009) Volumetric and anatomical MRI hypoxic-ischemic encephalopathy: relationship to hypothermia therapy and neurosensory impairments. J Perinatol 29:143–149
Radi R (1991) Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481–487
Raichle ME (1983) The pathophysiology of brain ischemia. Ann Neurol 13:2–10
Ravishankar S, Ashraf QM, Mishra OP et al (2001) Expression of Bax and Bcl-2 proteins during hypoxia in cerebral cortical neuronal nuclei of newborn piglets: effect of administration of magnesium sulfate. Brain Res 901:23–29
Reed JC (1996) Mechanisms of Bcl-2 family protein function and dysfunction in health and disease. Behring Inst Mitt 97:72–100
Rosenbaum DM, Michaelson M, Batter DK et al (1994) Evidence for hypoxia induced programmed cell death of cultured neurons. Ann Neurol 25:19–33
Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19:105–111
Rouse D, Hirtz DG, Thom E et al (2008) A randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 359:895–905
Russell GA, Cooke RW (1995) Randomized controlled trial of allopurinol prophylaxis in very preterm infants. Arch Dis Child Fetal Neonatal Ed 73:F27–F31
Sahni R, Sanocka UM (2008) Hypothermia for hypoxic-ischemic encephalopathy. Clin Perinatol 35:717–734
Sawyer DT (1981) How super is superoxide? Acc Chem Res 14:393–400
Shankaran S, Laptook A, Wright LL et al (2002) Whole-body hypothermia for neonatal encephalopathy: animal observations as a basis for randomized, controlled pilot study in term infants. Pediatrics 110:377–385
Shankaran S, Laptook AR, Ehrenkranz RA et al (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584
Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K et al (2012) Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 366:2085–2092. https://doi.org/10.1056/NEJMoa1112066
Tacconi S, Ratti E, Marien MR et al (1993) Inhibition of (3H)- (+)-MK-801 binding to rat brain sections by CPP and 7-chlorokynurenic acid: an autoradiographic analysis. Br J Pharmacol 108:668–674
Talati AJ, Yang W, Yolton K et al (2005) Combination of early perinatal factors to identify near-term and term neonates for neuroprotection. J Perinatol 25:245–250
Tan S, Parks DA (1999) Preserving brain function during neonatal asphyxia. Clin Perinatol 26:733–747
Tang YP, Shimizu E, Dube GR et al (1999) Genetic enhancement of learning and memory in mice. Nature 401:63–69
The Eclampsia Trial Collaborative Group (1995) Which anticonvulsant for eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 345:1455–1463
Thorensen M, Penrice J, Lorek A (1995) Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet. Pediatr Res 37:667–670
Tominaga T, Kagure S, Narisawa K et al (1993) Endonuclease activation following focal ischemic injury in the rat brain. Brain Res 608:21–26
Trescher WH, Ishiwa S, Johnston MV (1997) Brief post-HI hypothermia markedly delays neonatal brain injury. Brain Dev 19:326–328
Van Bel F, Groenendaal F (2008) Long-term pharmalogic neuroprotection after birth asphyxia: where do we stand? Neonatology 94:203–210
Van Bel F, Shadid M, Moison RM et al (1998) Effect of allopurinol on postasphyxial free radical formation, cerebral hemodynamics, and electrical brain activity. Pediatrics 101:185–193
Vannucci RC (1990) Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage. Pediatr Res 27:317–326
Volpe J (2001) Neurology of the newborn, 3rd edn. WB Saunders, Philadelphia
Wagner CL, Eicher DJ, Katikkaneni LD et al (1999) The use of hypothermia: a role in the treatment of neonatal asphyxia? Pediatr Neurol 21:429–443
Wagner BP, Nedelcu J, Martin E (2002) Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats. Pediatr Res 51:182–193
Waseem W, Ashraf QM, Zanelli SA et al (2001) Effect of graded hypoxia on cerebral cortical genomic DNA fragmentation in newborn piglet. Biol Neonate 79:187–193
Williams GD, Palmer C, Heitjan DF et al (1992) Allopurinol preserves cerebral energy metabolism during perinatal hypoxic-ischemia: a 31P NMR study in anaesthetized immature rats. Neurosci Lett 144:104–106
Wylie AH, Kerr JFR, Currie AR (1980) Cell Death, the significance of apoptosis. Int Rev Cytol 68:251–306
Yamakura T, Sakimura K, Shimoji K (1999) Direct inhibition of the N-methyl-D-aspartate receptor channel by high concentration of opioids. Anesthesiology 91:1053–1063
Zanelli SA (1999) NMDA receptor-mediated calcium influx in cerebral cortical synaptosomes of the hypoxic guinea pig fetus. Neurochem Res 24:434–446
Zanelli SA, Ashraf QM, Mishra OP (2002) Nitration is a mechanism of regulation of the NMDA receptor function during hypoxia. Neuroscience 112:869–877
Zanelli SA, Naylor M, Dobbins N et al (2008) Implementation of a “hypothermia for HIE” program: 2-year experience in a single NICU. J Perinatol 28:171–175
Zhang J, Haddad GG, Xia Y (2000) Delta-, but not mu- and kappa, opioid receptor activation protects neocortical neurons from glutamate- induced excitotoxic injury. Brain Res 885:143–153
Zhang J, Gibney GT, Zhao P (2002) Neuroprotective role of delta opioid receptors in cortical neurons. Am J Physiol 282:C1225–C1234
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Delivoria-Papadopoulos, M., Kratimenos, P., Anday, E.K. (2018). Biochemical Basis of Hypoxic-Ischemic Encephalopathy. In: Buonocore, G., Bracci, R., Weindling, M. (eds) Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29489-6_272
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