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Section 1 - Epidemiology, Pathophysiology, and Pathogenesis of Fetal and Neonatal Brain Injury

Published online by Cambridge University Press:  13 December 2017

Edited by
David K. Stevenson ,
William E. Benitz ,
Philip Sunshine ,
Susan R. Hintz  and
Maurice L. Druzin
David K. Stevenson
Affiliation:
Stanford University, California
William E. Benitz
Affiliation:
Stanford University, California
Philip Sunshine
Affiliation:
Stanford University, California
Susan R. Hintz
Affiliation:
Stanford University, California
Maurice L. Druzin
Affiliation:
Stanford University, California
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Fetal and Neonatal Brain Injury , pp. 1 - 66
Publisher: Cambridge University Press
Print publication year: 2017

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References

References

Stanley, F, Blair, E, Alberman, E. Cerebral Palsies: Epidemiology and Causal Pathways (Clinics in Developmental Medicine 151). London: MacKeith Press, 2000.Google Scholar
Nelson, KB, Leviton, A. How much of neonatal encephalopathy is due to birth asphyxia? Am J Dis Child 1991; 145: 1325–31.Google Scholar
Gaffney, G, Flavell, V, Johnson, A, et al. Cerebral palsy and neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed 1994; 70: F195–200.Google Scholar
Perlman, JM, Risser, R. Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers? Pediatrics 1996; 97: 456–62.Google Scholar
Badawi, N, Kurinczuk, JJ, Keogh, JM, et al. Intrapartum risk factor for newborn encephalopathy: the Western Australian case control study. BMJ 1998; 317: 1554–8.Google Scholar
Nelson, KB, Grether, JK. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. Am J Obstet Gynecol 1998; 179: 507–13.Google Scholar
MacLennan, A. A template for defining a causal relationship between acute intrapartum events and cerebral palsy: international consensus statement International Cerebral Palsy Task Force. BMJ 1999; 319: 1054–9.Google Scholar
Phelan, JP, Kim, JO. Fetal heart rate observations in the brain damaged infant. Semin Perinatol 2000; 24: 221–9.Google Scholar
Hankins, GDV, Speer, M. Defining the pathogenesis and pathophysiology of neonatal encephalopathy and cerebral palsy. Obstet Gynecol 2003; 102: 628–36.Google ScholarPubMed
American College of Obstetricians and Gynecologists, American Academy of Pediatrics. Neonatal Encephalopathy and Neurologic Outcome, 2nd edn. Washington, DC: ACOG, 2014.Google Scholar
Cowan, F, Rutherford, M, Groenendaal, F, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003; 361: 736–42.Google Scholar
Shevell, MI. The “Bermuda Triangle” of neonatal neurology: cerebral palsy, neonatal encephalopathy, and intrapartum asphyxia. Semin Pediatr Neurol 2004; 11: 24–30.Google Scholar
Perlman, JM. Brain injury in the term infant. Semin Perinatol 2004; 28: 415–24.CrossRefGoogle ScholarPubMed
Ferriero, DM. Neonatal brain injury. N Engl J Med 2004; 351: 1985–95.Google Scholar
Bartha, AI, Foster-Barber, A, Miller, SP, et al. Neonatal encephalopathy: association of cytokines and MR spectroscopy and outcome. Pediatr Res 2004; 56: 960–6.Google Scholar
Becher, JC, Bell, JE, Keeling, JW, et al. The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths. Arch Dis Child Fetal Neonatal Ed 2004; 89: F399–407.Google Scholar
Low, JA. Determining the contribution of asphyxia to brain damage in the neonate. J Obstet Gynaecol Res 2004; 30: 276–86.CrossRefGoogle ScholarPubMed
Pierrat, V, Haouari, N, Liska, A, et al. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population-based study. Arch Dis Child Fetal Neonatal Ed 2005; 90: F257–61.CrossRefGoogle ScholarPubMed
Badawi, N, Felix, JF, Kurinczuk, JJ, et al. Cerebral palsy following term newborn encephalopathy: a population-based study. Dev Med Child Neurol 2005; 47: 293–8.Google Scholar
Foley, ME, Alarab, M, Daly, L, et al. Term neonatal asphyxial seizures and peripartum deaths: lack of correlation with a rising cesarean delivery rate. Am J Obstet Gynecol 2005; 192: 102–8.Google Scholar
Haider, BA, Bhutta, ZA. Birth asphyxia in developing countries: current status and public health implications. Curr Probl Pediatr Adolesc Health Care 2006; 36: 178–88.Google Scholar
Thorngren-Jerneck, K, Herbst, A. Perinatal factors associated with cerebral palsy in children born in Sweden. Obstet Gynecol 2006; 108: 1499–505.Google Scholar
Perlman, JM. Intrapartum asphyxia and cerebral palsy: is there a link? Clin Perinatol 2006; 33: 335–53.Google Scholar
Bercher, JC, Stenson, B, Lyon, A. Is intrapartum asphyxia preventable? BJOG 2007; 114: 1442–4.Google Scholar
Flidel-Rimon, O, Shinwell, ES. Neonatal aspects of the relationship between intrapartum events and cerebral palsy. Clin Perinatol 2007; 34: 439–49.CrossRefGoogle ScholarPubMed
Milsom, I, Ladfors, L, Thiringer, K, et al. Influence of maternal, obstetric and fetal risk factors on the prevelance of birth asphyxia at term in a Swedish urban population. Acta Obstet Gynecol Scand 2002; 81: 909–17.Google Scholar
Hogan, L, Ingemarsson, I, Thorngren-Jerneck, K, et al. How often is a low 5-min Apgar score in term infants due to asphyxia? Eur J Obstet Gynecol Reprod Biol 2007; 130: 169–75.CrossRefGoogle ScholarPubMed
Rennie, JM, Hagmann, CF, Robertson, NJ. Outcome after intrapartum hypoxic ischemia at term. Semin Fetal Neonatal Med 2007; 12: 398–407.Google Scholar
Volpe, JJ. Hypoxic-ischemic encephalopathy. In Volpe, JJ, ed., Neurology of the Newborn, 5th edn. Philadelphia: Saunders/Elsevier, 2008: 400–80.Google Scholar
Eicher, DJ, Wagner, CL, Katikaneni, LP, et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005; 32: 11–17.CrossRefGoogle ScholarPubMed
Gluckman, PD, Wyatt, JS, Azzopardi, D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365: 663–70.CrossRefGoogle ScholarPubMed
Shankaran, S, Laptook, AR, Ehrenkranz, RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353: 1574–84.Google Scholar
Azzopardi, DV, Strohm, B, Edwards, AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361: 1349–58.Google Scholar
Simbruner, G, Mittal, RA, Rohlmann, F, Muche, R. Systemic hypothermia after neonatal encephalopathy. Pediatrics 2010; 126: e771–8.Google Scholar
Zhou, WH, Cheng, GQ, Shao, XM, et al. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr 2010; 157: 367–72.Google Scholar
Tagin, MA, Woolcott, CG, Vincer, MJ, et al. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med 2012; 166: 558–66.CrossRefGoogle ScholarPubMed
Takenouchi, T, Iwata, O, Nabetani, M, Tamura, M. Therapeutic hypothermia for neonatal encephalopathy: JSPNM&MHLW Japan Working Group Practice Guidelines Consensus Statement from the Working Group on Therapeutic Hypothermia for Neonatal Encephalopathy, Ministry of Health, Labor and Welfare (MHLW), Japan, and Japan Society for Perinatal and Neonatal Medicine (JSPNM). Brain Dev 2012; 34: 165–70.Google Scholar
Jacobs, SE, Morley, CJ, Inder, TE. 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.CrossRefGoogle ScholarPubMed
Jacobs, SE, Berg, M, Hunt, R, et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev 2013; 1: CD003311.Google Scholar
Committee on Obstetric Practice, American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 326, December 2005. Inappropriate use of the terms fetal distress and birth asphyxia. Obstet Gynecol 2005; 106: 1469–70.Google Scholar
Volpe, JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol 2012; 72: 156–66.Google Scholar
Wu, Y. Brain injury in newborn babies: we can’t afford to get it wrong. Ann Neurol 2012; 72: 151.Google Scholar
Harteman, JC, Nikkels, PGJ, Benders, MJNL, et al. Placental pathology in full-term infants with hypoxic-ischemic neonatal encephalopathy and association with magnetic resonance imaging pattern of brain injury. J Pediatr 2013; 163: 968–75.Google Scholar
Chang, KT. Examination of the placenta: medico-legal implications. Semin Fetal Neonatal Med 2014; 19: 279–84.Google Scholar
Nasiell, J, Papadogiannakis, N, Lof, E, et al. Hypoxic ischemic encephalopathy in newborns linked to placental and umbilical cord abnormalities. J Matern Fetal Neonatal Med 2015; 5: 1–6.Google Scholar
Lachapelle, J, Chen, M, Oskoui, M, et al. Placental pathology in asphyxiated newborns treated with therapeutic hypothermia. J Neonatal Perinatal Med 2015; 8: 33–40.CrossRefGoogle Scholar
Clarke, P, Gardner, D, Venkatesh, V, et al. Investigation of neonatal encephalopathy: the oft-lost placental “black box.” Pediatr Dev Pathol 2015; 18: 343–4.CrossRefGoogle ScholarPubMed
Myers, RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol 1972; 112: 246–76.Google Scholar
Mallard, EC, Williams, CE, Johnston, BM, et al. Repeated episodes of umbilical cord occlusion in fetal sheep lead to preferential damage to the striatum and sensitize the heart to further insults. Pediatr Res 1995; 37: 707–13.Google Scholar
Ghei, SK, Zan, E, Nathan, JE, et al. MR imaging of hypoxic-ischemic injury in term neonates: pearls and pitfalls. Radiographics 2014; 34: 1047–61.Google Scholar
Leung, AS, Leung, EK, Paul, RH. Uterine rupture after previous cesarean delivery: maternal and fetal consequences. Am J Obstet Gynecol 1993; 169: 945–50.Google Scholar
Lee, ACC, Kozuki, N, Blencowe, H, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res 2013; 74: 50–72.Google Scholar
Thornberg, E, Thiringer, K, Odeback, A, Milsom, I. Birth asphyxia: incidence, clinical course and outcome in a Swedish population. Acta Paediatr 1995; 84: 927–32.CrossRefGoogle Scholar
Graham, EM, Ruis, KA, Hartman, AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199: 587–95.Google Scholar
Lee, AC, Kozuki, N, Blencowe, H, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res 2013; 74: 50–72.CrossRefGoogle ScholarPubMed
American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy. Executive summary: neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy. Obstet Gynecol 2014; 123: 896–901.Google Scholar
Sarnat, HB, Sarnat, MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol 1976; 33: 696–705.Google Scholar
Wu, YW, Backstrand, KH, Zhao, S, et al. Declining diagnosis of birth asphyxia in California: 1991–2000. Pediatrics 2004; 114: 1584–90.Google Scholar
Martin, JA, Kochanek, KD, Strobino, DM, et al. Annual summary of vital statistics: 2003. Pediatrics 2005; 115: 619–34.Google Scholar
Hayakawa, M, Ito, Y, Saito, S, et al. Incidence and prediction of outcome in hypoxic-ischemic encephalopathy in Japan. Pediatr Int 2014; 56: 215–21.Google Scholar
Locatelli, A, Incerti, M, Paterlini, G, et al. Antepartum and intrapartum risk factors for neonatal encephalopathy at term. Am J Perinatol 2010; 27: 649–54.Google Scholar
Nelson, KB, Bingham, P, Edwards, EM, et al. Antecedents of neonatal encephalopathy in the Vermont Oxford Network Encephalopathy Registry. Pediatrics 2012; 130: 878–86.Google Scholar
Hayes, BC, McGarvey, C, Mulvany, S, et al. A case-control study of hypoxic-ischemic encephalopathy in newborn infants at >36 weeks’ gestation. Am J Obstet Gynecol 2013; 209: e1–29.CrossRefGoogle ScholarPubMed
Martinez-Biarge, M, Diez-Sebastian, J, Wusthoff, CJ, et al. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics 2013; 132: e952–9.Google Scholar
Nelson, KB, Ellenberg, JH. Obstetric complications as risk factors for cerebral palsy or seizure disorders. JAMA 1984; 251: 1843–8.Google Scholar
Blair, E, Al Asedy, F, Badawi, N, et al. Is cerebral palsy associated with birth defects other than cerebral defects? Dev Med Child Neurol 2007; 49: 252–8.Google Scholar
Kahana, B, Sheiner, E, Levy, A, et al. Umbilical cord prolapse and perinatal outcomes. Int J Gynaecol Obstet 2004; 84: 127–32.Google Scholar
Wu, YW, Escobar, GJ, Grether, JK, et al. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA 2003; 290: 2677–84.Google Scholar
Tekgul, H, Yalaz, M, Kutukculer, N, et al. Value of biochemical markers for outcome in term infants with asphyxia. Pediatr Neurol 2004; 31: 326–32.Google Scholar
Ramaswamy, V, Horton, J, Vandermeer, B, et al. Systematic review of biomarkers of brain injury in term neonatal encephalopathy. Pediatr Neurol 2009; 40: 215–26.Google Scholar
Kasdorf, E, Perlman, J. Hyperthermia, inflammation, and perinatal brain injury. Pediatr Neurol 2013; 49: 8–14.CrossRefGoogle ScholarPubMed
Jenster, M, Bonifacio, SL, Ruel, T, et al. Maternal or neonatal infection: association with neonatal encephalopathy outcomes. Pediatr Res 2014; 76: 93–9.Google Scholar
Nelson, KB, Penn, AA. Is infection a factor in neonatal encephalopathy? Arch Dis Child Fetal Neonatal Ed 2015; 100: F8–10.Google Scholar
O’Hare, FM, Watson, RWG, O’Neill, A, et al. Persistent systemic monocyte and neutrophil activation in neonatal encephalopathy. J Matern Fetal Neonatal Med 2016; 29: 582–9.Google Scholar
Hagberg, H, Mallard, C, Ferriero, DM, et al. The role of inflammation in perinatal brain injury. Nat Rev 2015; 11: 192–208.Google Scholar
Apgar, VA. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 1953; 32: 260–7.Google Scholar
Odd, DE, Lewis, G, Whitelaw, A, Gunnell, D. Resuscitation at birth and cognition at 8 years of age: a cohort study. Lancet 2009; 373: 1615–22.CrossRefGoogle ScholarPubMed
Natarajan, G, Hankaran, S, Laptook, AR, et al. Apgar scores at 10 min and outcomes at 6–7 years following hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2013; 98: F473–9.Google Scholar
Shah, P, Anvekar, A, McMichael, J, Rao, S. Outcomes of infants with Apgar score of zero at 10 min: the West Australian experience. Arch Dis Child Fetal Neonatal Ed 2015; 100: F492–4.Google Scholar
Kasdorf, E, Laptook, A, Azzopardi, D, et al. Improving infant outcome with a 10 min Apgar of 0. Arch Dis Child Fetal Neonatal Ed 2015; 100: F102–5.CrossRefGoogle ScholarPubMed
Dijxhoorn, MJ, Visser, GHV, Touwen, BC. Apgar score, meconium and acidemia at birth in small to gestational age infants born at term, and their relationship to neonatal neurological morbidity. Br J Obstet Gynaecol 1987; 94: 873–9.CrossRefGoogle Scholar
Grant, A, O’Brien, W, Joy, MT, et al. Cerebral palsy among children born during the Dublin randomised trial of intrapartum monitoring. Lancet 1989; 2: 1233–6.Google Scholar
Alfirevic, Z, Devane, D, Gyte, GM. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring for fetal assessment during labour. Cochrane Database Syst Rev 2013; CD006066.Google Scholar
Chauhan, SP, Hendrix, NW, Magann, EF, et al. Neonatal organ dysfunction among newborns at gestational age ≥ 34 weeks, and umbilical arterial pH < 7.00. J Matern Fetal Neonatal Med 2005; 17: 261–8.Google Scholar
Goodwin, TM, Belai, I, Hernandez, P, et al. Asphyxial complications in the term newborn with severe umbilical acidemia. Am J Obstet Gynecol 1992; 167: 1506–12.Google Scholar
Belai, Y, Goodwin, TM, Durand, M, et al. Umbilical arteriovenous PO2 and PCO2 differences and neonatal morbidity in term infants with severe acidosis. Am J Obstet Gynecol 1998; 178: 13–19.Google Scholar
Tekgul, H, Gauvreau, K, Soul, J, et al. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics 2006; 117: 1270–80.Google Scholar
Bonifacio, SL, deVries, LS, Groenendaal, F. Impact of hypothermia on predictors of poor outcome: how do we decide to redirect care? Sem Fetal Neonatal Med 2015; 20: 122–7.CrossRefGoogle ScholarPubMed
Shetty, J. Neonatal seizures in hypoic-ischaemic encephalopathy: risks and benefits of anticonvulasant therapy. Dev Med Child Neurol 2015; 57: 40–3.Google Scholar
Silverstein, FS, Jensen, FE. Neonatal seizures. Ann Neurol 2007; 62: 112–20.Google Scholar
Miller, SP, Weiss, J, Barnwell, A, et al. Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology 2002; 58: 542–8.Google Scholar
Hankins, GDV, Koen, S, Gei, F, et al. Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstet Gynecol 2002; 99: 688–91.Google Scholar
Shah, P, Riphagen, S, Beyene, J, et al. Multiorgan dysfunction in infants with post-asphyxial hypoxic–ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2004; 89: F152–5.Google Scholar
Carter, BS, Haverkamp, AD, Merenstein, GB. The definition of acute perinatal asphyxia. Clin Perinatol 1993; 20: 287–304.Google Scholar
Clancy, RR, Sladky, JT, Rorke, LB. Hypoxic-ischemic spinal cord injury following perinatal asphyxia. Ann Neurol 1989; 25: 185–9.Google Scholar
Phelan, JP, Ahn, MO, Korst, L, et al. Intrapartum fetal asphyxial brain injury with absent multi-organ system dysfunction. J Matern Fetal Med 1998; 7: 19–22.Google Scholar
Trevisanuto, D, Picco, G, Golin, R, et al. Cardiac troponin I in asphyxiated neonates. Biol Neonate 2006; 89: 190–3.Google Scholar
Thorngren-Jerneck, K, Alling, C, Herbst, A, et al. S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic ischemic encephalopathy. Pediatr Res 2004; 55: 406–12.Google Scholar
Douglas-Escobar, M, Yang, C, Bennett, J, et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr Res 2010; 68: 531–6.CrossRefGoogle ScholarPubMed
Ennen, CS, Huisman, TA, Savage, WJ, et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling. Am J Obstet Gynecol 2011; 205: e1–7.Google Scholar
Massaro, AN, Chang, T, Kadom, N, et al. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia. J Pediatr 2012; 161: 434–40.CrossRefGoogle ScholarPubMed
Massaro, AN, Jeromin, A, Kadom, N, et al. Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr Crit Care Med 2013; 14: 310–7.CrossRefGoogle ScholarPubMed
Chalak, LF, Sanchez, PJ, Adams-Huet, B, et al. Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy. J Pediatr 2014; 164: 468–74.Google Scholar
Ferriero, DM, Bonifacio, SL. The search continues for the elusive biomarkers of neonatal brain injury. J Pediatr 2014; 164: 438–9.Google Scholar
Bennet, L, Booth, L, Gunn, AJ. Potential biomarkers for hypoxic-ischemic encephalopathy. Semin Fetal Neonatal Med 2010; 15: 253–60.Google Scholar
Phelan, JP, Kirkendall, C, Korst, LM, et al. Nucleated red blood cell and platelet counts in asphyxiated neonates sufficient to result in permanent neurological impairment. J Matern Fetal Neonatal Med 2007; 20: 377–80.Google Scholar
Thompson, CM, Puterman, As, Linley, LL, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr 1997; 86: 757–61.CrossRefGoogle ScholarPubMed
Committee on Fetus and Newborn, Papile, LA, Baley, JE, et al. Hypothermia and neonatal encephalopathy. Pediatrics 2014: 133: 1146–50.Google Scholar
Nanavati, T, Seemaladinne, N, Regier, M, et al. Can we predict functional outcome in neonates with hypoxic ischemic encephalopathy by the combination of neuroimaging and electroencephalography? Pediatr Neonatol 2015; 56: 307–16.Google Scholar
Hayes, BC, Ryan, S, McGarvey, C, et al. Brain magnestic resonance imaging and outcome after hypoxic ischaemic encephalopathy. J Matern Fetal Neonatal Med 2016; 29: 777–82.CrossRefGoogle Scholar
Skranes, JH, Cowan, FM, Stiris, T, et al. Brain imaging in cooled encephalopathic neonates does not differ between four and 11 days after birth. Acta Paediatr 2015; 104: 752–8.Google Scholar
McIntyre, S, Blair, E, Badawi, N, et al. Antecedents of cerebral palsy and perinatal death in term and late preterm singletons. Obstet Gynecol 2013; 122: 869–77.Google Scholar
Perlman, J, Davis, P, Wyllie, J, Kattwinkel, J. Therapeutic hypothermia following intrapartum hypoxia-ischemia: an advisory statement from the Neonatal Task Force of the International Liaison Committee on Resuscitation. Resuscitation 2010; 81: 1459–61.Google Scholar
Shankaran, S, Laptook, AR, Pappas, A, et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic-ischemic encephalopathy. JAMA 2014; 312: 2629–39.CrossRefGoogle ScholarPubMed
Gunes, T, Ozturk, MA, Koklu, E, et al. Effect of allopurinol supplementation on nitric oxide levels in asphyxiated newborns. Pediatr Neurol 2007; 36: 17–24.Google Scholar
Glass, HC, Ferriero, DM. Treatment of hypoxic-ischemic encephalopathy in newborns. Curr Treat Options Neurol 2007; 9: 414–23.Google Scholar
Zhu, C, Kang, W, Xu, F, et al. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics 2009; 124: e218–26.Google Scholar
Li, J, McDonald, CA, Fahey, MC, et al. Could cord blood cell therapy reduce preterm brain injury? Front Neurol 2014; 5: 200.Google Scholar
Cotton, MC, Murtha, AP, Goldberg, RN, et al., Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr 2014; 164: 973–9.Google Scholar
Shankaran, S, Laptook, AR, Pappas, A, et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA 2014; 312: 2629–39.Google Scholar
Rogers, EE, Bonifacio, SL, Glass, HC, et al. Erythropoietin and hypothermia for hypoxic-ischemic encephalopathy. Pediatr Neurol 2014; 51: 657–62.Google Scholar
Kasdorf, E, Perlman, JM. Strategies to prevent reperfusion injury to the brain following intrapartum hypoxia-ischemia. Semin Fetal Neonatal Med 2013; 18: 379–84.Google Scholar
Van Velthoven, CTJ, Gonzalez, F, Vexler, ZS, Ferriero, DM. Stem cells for neonatal stroke- the future is here. Front Cell Neurosci 2014; 8: 207.Google Scholar
Rangarajan, V, Juul, SE. Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection. Pediatr Neurol 2014; 51: 481–8.Google Scholar
Shea, KL, Palanisamy, A. What can you do to protect the newborn brain? Curr Opin Anesthesiol 2015 (epub ahead of print).Google Scholar
Aly, H, Elmahdy, H, El-Dib, M, et al. Melatonin use for neuroprotection in perinatal asphyxia: a randomized, controlled pilot study. J Perinatol 2015; 35: 186–91.Google Scholar
Ellenberg, JH, Nelson, KB. The association of cerebral palsy with birth asphyxia: a definitional quaqmire. Dev Med Child Neurol 2013; 55: 210–16.Google Scholar
Yeargin-Allsopp, M, Van Naarden Braun, K, Doernberg, NS, et al. Prevalence of cerebral palsy in 8-year-old children in three areas of the United States in 2002: a multisite collaboration. Pediatrics 2008; 121: 547–54.Google Scholar
Oskoui, M, Coutinho, F, Dykeman, J, et al. An update on the prevalence of cerebral palsy: a systematic review and meta-analysis. Dev Med Child Neurol 2013; 55: 509–19.Google Scholar
Himmelmann, K, Hagberg, G, Beckung, E, et al. The changing panorama of cerebral palsy in Sweden. IX. Prevalence and origin in the birth year period 1995–1998. Acta Paediatr 2005; 94: 287–94.CrossRefGoogle ScholarPubMed
Himmelmann, K. Epidemiology of cerebral palsy. In Handbook Clinical Neurology, vol. III: Pediatric Neurology Part I, d. Duke, OF, Lassonde, M, Sarnat, HB. New York: Elsivier, 2013: 163–7.Google Scholar
Himmelmann, K, Uvebrant, P. The panorama of cerebral palsy in Sweden. XI. Changing patterns in the birth-year period 2003–2006. Acta Paediatr 2014; 103: 618–24.Google Scholar
Bax, M, Tydeman, C, Flodmark, O. Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. JAMA 2006; 296: 1602–8.Google Scholar
Wu, YW, Croen, LA, Shah, SJ, et al. Cerebral palsy in a term population: risk factors and neuroimaging findings. Pediatrics 2006; 118: 690–7.Google Scholar
Blair, EM, Nelson, KB. Fetal growth restriction and risk of cerebral palsy in singletons born after at least 35 weeks’ gestation. Am J Obstet Gynecol 2015; 520: e1–7.Google Scholar
Himmelmann, K, Hagberg, G, Wiklund, LM, et al. Dyskinetic cerebral palsy: a population-based study of children born between 1991 and 1998. Dev Med Child Neurol 2007; 49: 246–51.Google Scholar
Tollanes, MC, Wilcox, AJ, Lie, RT, Moster, D. Familial risk of cerebral palsy: population based cohort study. BMJ 2014; 349: 4294–301.Google Scholar
Hirvonen, M, Ojala, R, Korhonen, P, et al. Cerebral palsy among children born moderately and late preterm. Pediatrics 2014; 134: e1584–93.Google Scholar
Nelson, K. infection in pregnancy and cerebral palsy. Dev Med Child Neurol 2009; 51: 252–5.Google Scholar
Nelson, KB, Penn, AA. Is infection a factor in neonatal encephalopathy? Arch Dis Child Fetal Neonatal Ed 2015; 100: F8–10.Google Scholar
O’Leary, CM, Watson, L, D’Antoine, H, et al. Heavy maternal alcohol consumption and cerebral palsy in the offspring. Dev Med Child Neurol 2012; 54: 224–30.Google Scholar
Nelson, KB. Preventing cerebral palsy: paths not (yet) taken. Dev Med Child Neurol 2009; 51: 765–6.Google Scholar
Garfinkle, J, Wintermark, P, Shevell, MI, et al. Cerebral palsy after neonatal encephalopathy: how much is preventable. J Pediatr 2015; 167: 58–63.CrossRefGoogle ScholarPubMed
Nelson, KB. Can we prevent cerebral palsy? N Engl J Med 2003; 349: 1765–9.Google Scholar
Nelson, KB. The epidemiology of cerebral palsy in term infants. Ment Retard Dev Disabil Res Rev 2002; 8: 146–50.Google Scholar
Blair, E, Watson, L. Epidemiology of cerebral palsy. Semin Fetal Neonatal Med 2006; 11: 117–25.Google Scholar
Clark, SL, Hankins, GDV. Temporal and demographic trends in cerebral palsy: fact and fiction. Am J Obstet Gynecol 2003; 188: 628–33.Google Scholar
Landon, MB, Haut, JC, Leveno, KJ, et al. Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery. N Engl J Med 2004; 351: 2581–9.Google Scholar
Hankins, GDV, Clark, SM, Munn, MB. Cesarean section on request at 39 weeks: impact on shoulder dystocia, fetal trauma, neonatal encephalopathy, and intrauterine demise. Semin Perinatol 2006; 30: 276–87.CrossRefGoogle Scholar
Hagberg, B, Kyllerman, M. Epidemiology of mental retardation: a Swedish survey. Brain Dev 1983; 5: 441–9.Google Scholar
Robertson, CMT. Can hypoxic-ischemic encephalopathy (HIE) associated with term birth asphyxia lead to mental disability without cerebral palsy? Can J Neurol Sci 1999; 26: S36.Google Scholar
Gonzalez, FF, Miller, SP. Does perinatal asphyxia impair cognitive function without cerebral palsy? Arch Dis Child Fetal Neonatal Ed 2006; 91: F454–9.Google Scholar

References

Volpe, JJ. Neurology of the Newborn, 4th ed. Philadelphia: Saunders, 2001: 912.Google Scholar
Wu, TW, Backstrand, KH, Zhao, S, et al. Declining diagnosis of birth asphyxia in California: 1991–2000. Pediatrics 2004; 114: 1584–90.Google Scholar
Johnston, MV, Hoon, AH. Cerebral palsy. NeuroMolecular Med 2006; 8: 435–50.Google Scholar
Dilenge, M-E, Majnemer, A, Shevell, MI. Long-term developmental outcome of asphyxiated term neonates. J Child Neurol 2001; 16: 781–92.CrossRefGoogle ScholarPubMed
Graham, EM, Ruis, KA, Hartman, AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199: 587–95.Google Scholar
Hsia, T-Y, Gruber, PJ. Factors influencing neurologic outcome after neonatal cardiopulmonary bypass: what we can and cannot control. Ann Thorac Surg 2006; 81: S2381–88.Google Scholar
Maller, AI, Hankins, LL, Yeakley, JW, Butler, IJ. Rolandic type cerebral palsy in children as a pattern of hypoxic-ischemic injury in the full-term neonate. J Child Neurol 1998; 13: 313–21.Google Scholar
Ferriero, DM. Neonatal brain injury. N Engl J Med 2004; 351: 1985–95.Google Scholar
Martin, LJ, Brambrink, A, Koehler, RC, Traystman, RJ. Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia. J Comp Neurol 1997; 377: 262–85.Google Scholar
Martin, LJ, Brambrink, A, Koehler, RC, Traystman, RJ. Neonatal asphyxic brain injury is neural system preferential and targets sensory-motor networks. In Stevenson, DK, Sunshine, P, eds., Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risks of Practice, 2nd edn. New York: Oxford University Press, 1997: 374–99.Google Scholar
Myers, RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol 1972; 12: 246–76.Google Scholar
Johnston, MV, Nakajima, W, Hagberg, H. Mechanisms of hypoxic neurodegeneration in the developing brain. Neuroscientist 2002; 8: 212–20.Google Scholar
Martin, LJ. Mechanisms of brain damage in animal models of hypoxia-ischemia in newborns. In Stevenson, DK, Benitz, WE, Sunshine, P, eds., Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risks of Practice, 3rd edn. New York: Oxford University Press, 2003: 30–57.Google Scholar
McQuillen, PS, Ferriero, DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol 2004; 30: 227–35.Google Scholar
Blomgren, K, Hagberg, H. Free radicals, mitochondria, and hypoxia-ischemia in the developing brain. Free Rad Biol Med 2006; 40: 388–97.Google Scholar
Martin, LJ. Mitochondrial and cell death mechanisms in neurodegenerative diseases. Pharmaceuticals 2010; 3: 839–915.Google Scholar
Northington, FJ, Graham, EM, Martin, LJ. Apoptosis in perinatal hypoxic-ischemic brain injury: how important is it and should it be inhibited? Brain Res Rev 2005; 50: 244–57.Google Scholar
Chaudhari, T, McGuire, W. Allopurinol for preventing mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy. Cochrane Database of Systematic Reviews 2012; 7: CD006817. doi:10.1002/14651858.CD006817.pub3Google Scholar
Shah, PS. Hypothermia: a systemic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med 2010; 15: 238–46.Google Scholar
Wachtel, EV, Hendricks-Munzo, KD. Current management of the infant who presents with neonatal encephalopathy. Curr Probl Adolesc Health Care 2011; 4: 132–53.Google Scholar
Moler, FW, Silverstein, FS, Holubkov, R, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med 2015; 372: 1898–1908.Google Scholar
Haaland, K, Loberg, EM, Steen, PA, Thoresen, M. Posthypoxic hypothermia in newborn piglets. Pediatr Res 1997; 41: 505–12.Google Scholar
Agnew, DM, Koehler, RC, Guerguerian, AM, et al. Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming. Pediatr Res 2003; 54: 1–10.Google Scholar
Xiong, M, Cheng, GQ, Ma, SM, et al. Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain. Neurochem Int 2011; 58: 625–33.Google Scholar
Fukui, O, Kinugasa, Y, Fukuda, A, et al. Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain. Brain Res 2006; 1121: 35–45.Google Scholar
Martin, LJ, Al-Abdulla, NA, Brambrink, AM, et al. Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: a perspective on the contributions of apoptosis and necrosis. Brain Res Bull 1998; 46: 281–89.Google Scholar
Martin, LJ. Neuronal cell death in nervous system development, disease, and injury. Int J Mol Med 2001; 7: 455–78.Google Scholar
Wang, B, Armstrong, JS, Lee, J-H, et al. Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy. J Cereb Blood Flow Metab 2015; 35: 781–93.Google Scholar
Wang, B, Armstrong, JS, Reyes, M, et al. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy. Neuroscience 2016; 316:296–310.Google Scholar
Besancon, E, Guo, S, Lok, J, et al. Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke. Trends Pharmacol Sci 2008; 29: 268–75.Google Scholar
Martin, LJ. DNA damage and repair: relevance to mechanisms of neurodegeneration. J Neuropathol Exp Neurol 2008; 67: 377–87.Google Scholar
Narasimhaiah, R, Tuchman, A, Lin, SL, Naegele, JR. Oxidative damage and defective DNA repair is linked to apoptosis of migrating neurons and progenitors during cerebral cortex development in Ku70-deficient mice. Cerebral Cortex 2005; 15: 696–97.Google Scholar
Kraemer, KH, Patronas, NJ, Schiffmann, R, et al. Xeroderma pigmentosum, trichothiodystrophy and cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 2007; 145: 1388–96.Google Scholar
Rao, KS. Genomic damage and its repair in young and aging brain. Mol Neurobiol 1993; 7: 23–48.Google Scholar
Shiloh, Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 2003; 3: 155–68.Google Scholar
McKinnon, PJ. ATM and the molecular pathogenesis of ataxia telangiectasia. Annu Rev Pathol 2012; 7: 303–21.Google Scholar
Verhagen, MMM, Martin, J-J, van Deuren, M, et al. Neuropathology in classical and variant ataxia telangiectasia. Neuropathology 2012; 32: 234–44.Google Scholar
Englander, EW, Greeley, GH, Wang, G, et al. Hypoxia-induced mitochondrial and nuclear DNA damage in rat brain. J Neurosci Res 1999; 58: 262–69.Google Scholar
Ferrer, I, Tortosa, A, Macaya, A, et al. Evidence of nuclear DNA fragmentation following hypoxia-ischemia in the infant rat brain, and transient forebrain ischemia in the adult gerbil. Brain Pathol 1994; 4: 115–22.Google Scholar
Hill, IE, MacManus, JP, Rasquinha, I, Tuor, UI. DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxia-ischemia in the neonatal rat. Brain Res 1995; 676: 398–403.Google Scholar
de Torres, C, Munell, F, Ferrer, I, et al. Identification of necrotic cell death by the TUNEL assay in the hypoxic-ischemic neonatal rat brain. Neurosci Lett 1997; 230: 1–4.Google Scholar
Portera-Cailliau, C, Price, DL, Martin, LJ. Excitotoxic neuronal death in the immature brain is an apoptosis-necrosis morphological continuum. J Comp Neurol 1997; 378: 70–87.Google Scholar
MacManus, JP, Fliss, H, Preston, E, et al. Cerebral ischemia produces laddered DNA fragments distinct from cardiac ischemia and archetypal apoptosis. J Cereb Blood Flow Metab 1999;19: 502–10.Google Scholar
Huang, D, Shenoy, A, Cui, J, et al. In situ detection of AP sites and DNA strand breaks bearing 3’-phosphate termini in ischemic mouse brain. FASEB J 2000; 14: 407–17.Google Scholar
Lok, J, Martin, LJ. Rapid subcellular redistribution of bax precedes caspase-3 and endonuclease activation during excitotoxic neuronal apoptosis. J Neurotrauma 2002; 19: 815–28.Google Scholar
Gane, BD, Bhat, V, Rao, R, et al. Effect of therapeutic hypothermia on DNA damage and neurodevelopmental outcome among term neonates with perinatal asphyxia: a randomized controlled trial. J Trop Pediatr 2014; 60: 134–40.Google Scholar
Norbury, CJ, Hickson, ID. Cellular responses to DNA damage. Annu Rev Pharmacol Toxicol 2001; 41: 367–401.Google Scholar
Lindahl, T. Instability and decay of the primary structure of DNA. Nature 1993; 362: 709–15.Google Scholar
Juedes, MJ, Wogen, GN. Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells. Mutat Res 1996; 3349: 51–61.Google Scholar
Martin, LJ, Liu, Z. DNA damage profiling in motor neurons: a single-cell analysis by comet assay. Neurochem Res 2002; 27: 1093–1104.Google Scholar
Polyak, K, Xia, Y, Zweier, JL, et al. A model for p53-induced apoptosis. Nature 1997; 389: 300–5.Google Scholar
Kastan, MB, Lim, D-S. The many substrates and functions of ATM. Nat Rev Mol Cell Biol 2000; 1: 179–86.Google Scholar
Shangary, S, Brown, KD, Adamson, AW, et al. Regulation of DNA-dependent protein kinase activity by ionizing radiation-activated Abl kinase is an ATM-dependent process. J Biol Chem 2000; 275: 30161–68.Google Scholar
Nakagawa, K, Taya, Y, Tamai, K, Yamaizumi, M. Requirement of ATM in phosphorylation of the human p53 protein at serine 15 following DNA double-strand breaks. Mol Cell Biol 1999; 19: 2828–34.Google Scholar
Lee, Y, Chong, MJ, McKinnon, PJ. Ataxia telangiectasia mutated-dependent apoptosis after genotoxic stress in the developing nervous system is determined by cellular differentiation status. J Neurosci 2001; 21: 6687–93.Google Scholar
Kharbanda, S, Pandey, P, Yamauchi, T, et al. Activation of MEK kinase 1 by the c-Abl protein tyrosine kinase in response to DNA damage. Mol Cell Biol 2000; 20: 4070–89.Google Scholar
Lee, J-H, Paull, TT. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 2004; 304: 93–96.Google Scholar
Shiloh, Y. The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 2006; 31: 402–10.Google Scholar
Gorodetsky, E, Calkins, S, Ahn, J, Brooks, PJ. ATM, the Mre11/Rad50/Nbs1 complex, and topoisomerase 1 are concentrated in the nucleus of Purkinje neurons in the juvenile human brain. DNA Repair 2007; 6: 1698–1707.Google Scholar
Martin, LJ, Liu, Z, Pipino, J, et al. Molecular regulation of DNA damage-induced apoptosis in neurons of cerebral cortex. Cerebral Cortex 2009; 19: 1273–93.Google Scholar
Martin, LJ, Kaiser, A, Yu, JW, et al. Injury-induced apoptosis of neurons in adult brain is mediated by p53-dependent and p53-independent pathways and requires Bax. J Comp Neurol 2001; 433: 299–311.Google Scholar
Martin, LJ, Liu, Z. Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent. J Neurobiol 2002; 50: 181–97.Google Scholar
Martin, LJ, Price, AC, McClendon, K, et al. Early events in target deprivation/axotomy induced neuronal apoptosis in vivo: oxidative stress, DNA damage, p53 phosphorylation, and subcellular redistribution of death proteins. J Neurochem 2003; 85: 234–47.Google Scholar
Martin, LJ, Chen, K, Liu, Z. Adult motor neuron apoptosis is mediated by nitric oxide and Fas death receptor linked to DNA damage and p53 activation. J Neurosci 2005; 25: 6449–59.Google Scholar
Northington, F, Chavez-Valdez, R, Martin, LJ. Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol 2011; 69: 743–58.Google Scholar
Nijboer, CH, Heijnen, CJ, van der Kooij, MA, et al. Targeting the p53 pathway to protect the neonatal ischemic brain. Ann Neurol 2011; 70: 255–64.Google Scholar
Giaccia, AJ, Kastan, MB. The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 1998; 12: 2973–83.Google Scholar
Levine, AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323–31.CrossRefGoogle ScholarPubMed
Vogelstein, B, Kinzler, KW. p53 function and dysfunction. Cell 1992; 70: 523–36.Google Scholar
Slack, RS, Belliveau, DJ, Rosenberg, M, et al. Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons. J Cell Biol 1996; 135: 1085–96.Google Scholar
Cregan, SP, Arbour, NA, MacLaurin, JG, et al. p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death. J Neurosci 2004; 24: 10003–12.Google Scholar
Hsiang, YH, Hertzberg, R, Hecht, S, Liu, LF. Camptothecin induced protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985; 260: 14873–78.Google Scholar
Whitehouse, CJ, Taylor, RM, Thisthlethwaite, A, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001; 104: 107–17.Google Scholar
Binz, SK, Sheehan, AM, Wold, MS. Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair 2004; 3: 1015–24.Google Scholar
Zou, L, Elledge, SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003; 300: 1542–48.Google Scholar
Rothenberg, ML. Irinotecan (CPT-11): recent developments and future directions – colorectal cancer and beyond. Oncologist 2001; 6: 66–80.Google Scholar
Nieves-Neira, W, Pommier, Y. Apoptotic response to camptothecin and 7-hydroxystaurosporine (UCN-01) in the 8 human breast cancer cell lines of the NCI anticancer drug screen: multifactorial relationships with topoisomerase 1, protein kinase C, Bcl-2, p53, MDM-2 and caspase pathways. Int J Cancer 1999; 82: 396–404.Google Scholar
Bendixen, C, Thomsen, B, Alsner, J, Westergaard, O. Camptothecin-stabilized topoisomerase I-DNA adducts cause premature termination of transcription. Biochemistry 1990; 29: 5613–19.Google Scholar
Morris, EJ, Geller, HM. Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity. J Cell Biol 1996; 134: 757–70.Google Scholar
Lesuisse, C, Martin, LJ. Long term culture of mouse cortical neurons as a model for neuronal development, aging, and death. J Neurobiol 2002; 51: 9–23.Google Scholar
Lesuisse, C, Martin, LJ. Immature and mature cortical neurons engage different apoptotic mechanisms involving caspase-3 and the MAP kinase pathway. J Cereb Blood Flow Metab 2002; 22: 935–50.Google Scholar
Riva, D, Massimino, M, Giorgi, C, et al. Cognition before and after chemotherapy alone in children with chiasmatic-hypothalamic tumors. J Neurooncol 2009; 92: 49–56.Google Scholar
Stefanis, L, Park, DS, Friedman, WJ, Greene, LA. Caspase-dependent and -independent death of camptothecin-treated embryonic cortical neurons. J Neurosci 1999; 19: 6235–47.Google Scholar
Sordet, O, Khan, QA, Pommier, Y (2004) Apoptotic topoisomerase I-DNA complexes induced by oxygen radicals and mitochondrial dysfunction. Cell Cycle 2004; 3: 1095–97.Google Scholar
Takashima, H, Boerkoel, CF, Johns, J. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat Genet 2002; 32: 267–72.Google Scholar
Barthelmes, HU, Habermeyer, M, Christensen, MO, et al. TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerase I and II. J Biol Chem 2004; 279: 55618–25.Google Scholar
Hassine, SB, Arcangioli (2009) Tdp1 protects against oxidative DNA damage in non-dividing fission yeast. EMBO J 2009; 28: 632–40.Google Scholar
Keramaris, E, Stefanis, L, MacLaurin, J, et al. Involvement of caspase 3 in apoptotic death of cortical neurons evoked by DNA damage. Mol Cell Neurosci 2000; 15: 368–79.Google Scholar
Park, DS, Morris, EJ, Padmanabhan, J, et al. Cyclin-dependent kinases participate in death of neurons evoked by DNA-damaging agents. J Cell Biol 1998; 143: 457–67.Google Scholar
Endokido, Y, Araki, T, Tanaka, K, et al. Involvements of p53 in DNA strand break-induced apoptosis in postmitotic CNS neurons. Eur J Neurosci 1996; 8: 1812–21.Google Scholar
Burnsed, JC, Chavez-Valdez, R, Shanaz-Hossain, M, et al. Hypoxia-ischemia and therapeutic hypothermia in the neonatal mouse brain- a longitudinal study. PLoS One 2015;10(3): e0118889.doi:10.1371/journal.pone.0118889.Google Scholar
Martin, LJ, Liu, Z. Opportunities for neuroprotection in ALS using cell death mechanism rationales. Drug Discov Today Dis Models 2004; 1: 135–43.Google Scholar
Institute of Medicine. Neurodegeneration: Exploring Commonalities across Diseases. Workshop Summary. Washington, DC: National Academies Press, 2013: 93.Google Scholar
Martin, LJ. Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J Neuropathol Exp Neurol 1999; 58: 459–71.Google Scholar
Liu, Z, Martin, LJ. The olfactory bulb core is a rich source of neural progenitor and stem cells in adult rodent and human. J Comp Neurol 2003; 459: 368–91.Google Scholar
Martin, LJ, Katzenelson, A, Koehler, PC, Chang, Q. The olfactory bulb in newborn piglet is a reservoir of neural stem and progenitor cells. PLoS One 2013; 8(11): e81105. doi: 10.1371/journal.poneGoogle Scholar
Lai, H, Singh, NP. Acute low-intensity microwave exposure increased DNA single-strand breaks in rat brain cells. Bioelectromagnetics 1995; 16: 207–10.Google Scholar
Liu, Z, Martin, LJ. Isolation of mature spinal motor neurons and single cell analysis using the comet assay of early low-level DNA damage induced in vitro and in vivo. J Histochem Cytochem 2001; 49: 957–72.Google Scholar
Martin, LJ, Liu, Z. DNA damage profiling in motor neurons: a single-cell analysis by comet assay. Neurochem Res 2002; 27: 1093–1104.Google Scholar
Kohn, KW. Principles and practice of DNA filter elution. Pharmacol Ther 1991; 49: 55–77.Google Scholar
Ostling, O, Johanson, KJ. Microelectrophoretic study of radiation-induced DNA damage in individual mammalian cells. Biochem Biophys Res Commun 1984; 123: 291–98.Google Scholar
Schmidt, T, Korner, K, Karsunky, H, et al. The activity of the murine Bax promoter is regulated by Sp1/3 and E-box binding proteins but not by p53. Cell Death Diff 1999; 6: 873–82.Google Scholar
Igata, E, Inoue, T, Ohtani-Fujita, N, et al. Molecular cloning and functional analysis of the murine bax gene promoter. Gene 1999; 238: 407–15.Google Scholar
Horvath, MM, Wang, X, Resnick, MA, Bell, DA. Divergent evolution of human p53 binding sites: cell cycle versus apoptosis. PLoS Genet 2007; 3(7): e127. doi10.1371/journal.pgen.0030127Google Scholar
Odom, DT, Dowell, RD, Jacobsen, ES, et al. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 2007; 39: 730–32.Google Scholar
Fischer, H, Koenig, U, Eckhart, L, Tschachler, E. Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun 2002; 293: 722–26.Google Scholar
Ussat, S, Werner, U-E, Adam-Klages, SA. Species differences in the usage of several caspase substrates. Biochem Biophys Res Commun 2002; 297: 1186–90.Google Scholar
Kerr, LE, Birse-Archbold, J-LA, Simon, A, et al. Differential regulation of caspase-3 by pharmacological and developmental stimuli as demonstrated using humanized caspase-3 mice. Apoptosis 2004; 9: 739–47.Google Scholar
Jegga, AG, Inga, A, Menendez, D, et al. Functional evolution of the p53 regulatory network through its target response elements. Proc Natl Acad Sci USA 2008; 105: 944–9.Google Scholar
Laverdiere, M, Beaudoin, J, Lavigueur, A. Species-specific regulation of alternative splicing in the C-terminal region of the p53 tumor suppressor gene. Nucleic Acids Res 2000; 28: 1489–97.Google Scholar
Banuelos, CA, Banath, JP, MacPhail, SH, et al. Mouse but not human embryonic stem cells are deficient in rejoining of ionizing radiation-induced DNA double-strand breaks. DNA Repair 2008; 7: 1471–83.Google Scholar
Parrinello, S, Samper, E, Krtolica, A, et al. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 2003; 5: 741–47.Google Scholar
Barlow, C, Hirostune, S, Paylor, R, et al. ATM-deficient mice: a paradigm of ataxia telangiectasia. Cell 1997; 86: 159–71.Google Scholar
van der Horst, GTJ, van Steeg, H, Berg, RJW, et al. Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer. Cell 1997; 89: 425–35.Google Scholar
Jaarsma, D, van der Pluijm, I, de Waard, MC, et al. Age-associated neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology. PLoS Genet 2011; 7(12): e1002405. doi:10.1371/journal.pgen.1002405Google Scholar
Hirano, R, Interthal, H, Huang, C. et al. Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation? EMBO J 2007; 26: 4732–43.Google Scholar
Yang, H, Wang, G, Sun, H, et al. Species-dependent neuropathology in transgenic SOD1 pigs. Cell Res 2014; 24: 464–81.Google Scholar

References

Volpe, JJ. Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol 1998; 5(3): 135–51.Google Scholar
Ferriero, DM. Neonatal brain injury. N Engl J Med 2004; 351(19): 1985–95.Google Scholar
Vannucci, RC, Vannucci, SJ. A model of perinatal hypoxic-ischemic brain damage. Ann NY Acad Sci 1997; 835: 234–49.Google Scholar
Derugin, N, Ferriero, DM, Vexler, ZS. Neonatal reversible focal cerebral ischemia: a new model. Neurosci Res, 1998; 32(4)349–53.Google Scholar
Ashwal, S, et al. Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke 1998; 29(5)1037–46; discussion 1047.Google Scholar
McQuillen, PS, Ferriero, DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol 2004; 30(4)227–35.Google Scholar
Hagberg, H, Mallard, C. Effect of inflammation on central nervous system development and vulnerability. Curr Opin Neurol 2005; 18(2): 117–23.Google Scholar
Vexler, ZS. Glia and inflammation in neurodegenerative disease. In Yenari, MA, Giffard, RG, eds., Inflammation and Ischemia in the Developing Brain. Hauppauge, NY: Nova Science Publishers, 2006.Google Scholar
Vannucci, SJ, Hagberg, H. Hypoxia-ischemia in the immature brain. J Exp Biol 2004; 207(18): 3149–54.Google Scholar
Vexler, ZS, Tang, D, Yenari, M. Inflammation in adult and neonatal stroke. Clin Neurosci Res 2006: 6(5): 293–313.CrossRefGoogle ScholarPubMed
Northington, FJ, et al. Failure to complete apoptosis following neonatal hypoxia-ischemia manifests as “continuum” phenotype of cell death and occurs with multiple manifestations of mitochondrial dysfunction in rodent forebrain. Neuroscience 2007; 149(4)822–33.Google Scholar
Vannucci, RC, Vannucci, SJ. Glucose metabolism in the developing brain. Semin Perinatol 2000; 24(2): 107–15.Google Scholar
Perlman, JM. Intervention strategies for neonatal hypoxic-ischemic cerebral injury. Clin Ther 2006; 28(9): 1353–65.Google Scholar
Vexler, ZS, Ferriero, DM. Mechanisms of ischemic cell death in the developing brain, in Chan, P, ed., Handbook of Neurochemistry and Molecular Neurobiology. New York: Springer, 2006.Google Scholar
Rousset, CI, et al. A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischaemic brain injury in mice. J Neurochem 2015; 133(2)242–52.Google Scholar
Jiang, X, et al. Activated Src kinases interact with NMDA receptor after neonatal brain ischemia. Ann Neurol 2008; 63(5):632–41.Google Scholar
Fraser, M, et al. Extracellular amino acids and lipid peroxidation products in periventricular white matter during and after cerebral ischemia in preterm fetal sheep. J Neurochem 2008; 105(6): 2214–23.CrossRefGoogle ScholarPubMed
Sheldon, RA, Christen, S, Ferriero, DM. Genetic and pharmacologic manipulation of oxidative stress after neonatal hypoxia-ischemia. Int J Dev Neurosci 2007; 26(1): 87–92.Google Scholar
Ferriero, DM, et al. Neonatal mice lacking neuronal nitric oxide synthase are less vulnerable to hypoxic-ischemic injury. Neurobiol Dis 1996; 3(1): 64–71.Google Scholar
Drury, PP, et al. Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm fetal sheep. Exp Neurol 2013; 250: 282–92.Google Scholar
Bolton, SJ, Anthony, DC, Perry, VH. Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 1998; 86(4)1245–57.Google Scholar
Bazzoni, G, et al. Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin, and occludin. J Biol Chem 2000; 275(27): 20520–6.Google Scholar
Kratzer, I, Chip, S, Vexler, ZS. Barrier mechanisms in neonatal stroke. Front Neurosci 2014; 8: 359.Google Scholar
Garcia, JH, et al. Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol 1994; 144(1)188–99.Google Scholar
Hallenbeck, JM. Significance of the inflammatory response in brain ischemia. Acta Neurochir Suppl 1996; 66: 27–31.Google Scholar
Rosenberg, GA. Matrix metalloproteinases in neuroinflammation. Glia 2002; 39(3)279–91.Google Scholar
Allan, SM, Tyrrell, PJ, Rothwell, NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol 2005; 5(8): 629–40.Google Scholar
Pan, W, et al. Stroke upregulates TNF-α transport across the blood-brain barrier. Exp Neurol 2006; 198(1): 222–33.Google Scholar
Kniesel, U, Risau, W, Wolburg, H. Development of blood-brain barrier tight junctions in the rat cortex. Brain Res Dev Brain Res 1996; 96(1–2): 229–40.Google Scholar
Engelhardt, B. Development of the blood-brain barrier. Cell Tissue Res 2003; 314(1): 119–29.Google Scholar
Blamire, AM, et al. Interleukin-1β -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. J Neurosci 2000; 20(21): 8153–9.Google Scholar
Palmer, C, Roberts, RL, Young, PI. Timing of neutrophil depletion influences long-term neuroprotection in neonatal rat hypoxic-ischemic brain injury. Pediatr Res 2004; 55(4): 549–56.Google Scholar
Bona, E, et al. Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. Pediatr Res 1999; 45(4 Pt 1): 500–9.Google Scholar
Denker, S, et al. Macrophages are comprised of resident brain microglia not infiltrating peripheral monocytes acutely after neonatal stroke. J Neurochem 2007; 100(4): 893–904.Google Scholar
Svedin, P, et al. Matrix metalloproteinase-9 gene knock-out protects the immature brain after cerebral hypoxia-ischemia. J Neurosci 2007; 27(7): 1511–8.Google Scholar
Ranasinghe, HS, et al. Inhibition of MMP-9 activity following hypoxic ischemia in the developing brain using a highly specific inhibitor. Dev Neurosci 2012; 34(5): 417–27.Google Scholar
Raivich, G, et al. Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res Brain Res Rev 1999; 30(1): 77–105.Google Scholar
Monje, ML, Toda, H, Palmer, TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003; 302(5651): 1760–5.Google Scholar
Walton, NM, et al. Microglia instruct subventricular zone neurogenesis. Glia 2006; 54(8): 815–25.Google Scholar
Britschgi, M, Wyss-Coray, T. Immune cells may fend off Alzheimer disease. Nat Med 2007; 13(4): 408–9.Google Scholar
Marin-Teva, JL, et al. Microglia promote the death of developing Purkinje cells. Neuron 2004; 41(4): 535–47.Google Scholar
Derugin, N, et al. Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rat. Stroke 2000; 31: 1752–61.Google Scholar
McRae, A, et al. Microglia activation after neonatal hypoxic-ischemia. Brain Res Dev Brain Res 1995; 84(2): 245–52.Google Scholar
Dommergues, MA, et al. Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection. Neuroscience 2003; 121(3): 619–28.Google Scholar
Tikka, T, et al. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001; 21(8): 2580–8.Google Scholar
van den Tweel, ER, et al. Long-term neuroprotection with 2-iminobiotin, an inhibitor of neuronal and inducible nitric oxide synthase, after cerebral hypoxia-ischemia in neonatal rats. J Cereb Blood Flow Metab 2005; 25(1): 67–74.Google Scholar
Dingman, A, et al. Aminoguanidine inhibits caspase-3 and calpain activation without affecting microglial activation following neonatal transient ischemia. J Neurochem 2006; 96: 1467–79.Google Scholar
Faustino, JV, et al. Microglial cells contribute to endogenous brain defenses after acute neonatal focal stroke. J Neurosci 2011; 31(36): 12992–3001.Google Scholar
Dong, Y, Benveniste, EN. Immune function of astrocytes. Glia 2001; 36(2): 180–90.Google Scholar
Zhang, Y, et al. Notch-1 signaling regulates astrocytic proliferation and activation after hypoxia exposure. Neurosci Lett 2015; 603: 12–18.Google Scholar
Benveniste, EN. Cytokine actions in the central nervous system. Cytokine Growth Factor Rev 1998; 9(3–4): 259–75.Google Scholar
Teo, JD, Morris, MJ, Jones, NM. Hypoxic postconditioning reduces microglial activation, astrocyte and caspase activity, and inflammatory markers after hypoxia-ischemia in the neonatal rat brain. Pediatr Res 2015; 77(6): 757–64.Google Scholar
Iadecola, C, Zhang, F, Xu, X. Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am J Physiol 1995; 268(1 Pt 2): R286–92.Google Scholar
Nawashiro, H, et al. High susceptibility to cerebral ischemia in GFAP-null mice. J Cereb Blood Flow Metab 2000; 20(7): 1040–4.Google Scholar
Benjelloun, N, et al. Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal rat. Stroke 1999; 30(9): 1916–23; discussion 1923–4.Google Scholar
Benjelloun, N, et al. Apoptotic mitochondrial pathway in neurones and astrocytes after neonatal hypoxia-ischaemia in the rat brain. Neuropathol Appl Neurobiol 2003; 29(4): 350–60.Google Scholar
Ducrocq, S, et al. Poly(ADP-ribose) synthase inhibition reduces ischemic injury and inflammation in neonatal rat brain. J Neurochem 2000; 74(6): 2504–11.Google Scholar
Joly, LM, et al. Distribution of poly(ADP-ribosyl)ation and cell death after cerebral ischemia in the neonatal rat. Pediatr Res 2003; 53(5): 776–82.Google Scholar
Jin, Y, Silverman, AJ, Vannucci, SJ. Mast cell stabilization limits hypoxic-ischemic brain damage in the immature rat. Dev Neurosci 2007; 29(4–5): 373–84.Google Scholar
Patkai, J, et al. Deleterious effects of IL-9-activated mast cells and neuroprotection by antihistamine drugs in the developing mouse brain. Pediatr Res 2001; 50(2): 222–30.Google Scholar
Biran, V, et al. Stroke induces histamine accumulation and mast cell degranulation in the neonatal rat brain. Brain Pathol 2008; 18(1): 1–9.Google Scholar
Mesples, B, et al. Neuronal TGF-β1 mediates IL-9/mast cell interaction and exacerbates excitotoxicity in newborn mice. Neurobiol Dis 2005; 18(1): 193–205.Google Scholar
Hedtjarn, M, Mallard, C, Hagberg, H. Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia. J Cereb Blood Flow Metab 2004; 24(12): 1333–51.Google Scholar
Szaflarski, J, Burtrum, D, Silverstein, FS. Cerebral hypoxia-ischemia stimulates cytokine gene expression in perinatal rats. Stroke 1995; 26(6): 1093–100.Google Scholar
Dommergues, MA, et al. Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium. Ann Neurol 2000; 47(1): 54–63.Google Scholar
Fox, C, et al. Minocycline confers early but transient protection in the immature brain following focal cerebral ischemia-reperfusion. J Cereb Blood Flow Metab 2005; 25(9): 1138–49.Google Scholar
Mesples, B, Plaisant, F, Gressens, P. Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice. Brain Res Dev Brain Res, 2003; 141(1–2): 25–32.Google Scholar
Gerard, C, Rollins, BJ. Chemokines and disease. Nat Immunol 2001; 2(2): 108–15.Google Scholar
Hedtjarn, M, et al. Global gene expression in the immature brain after hypoxia-ischemia. J Cereb Blood Flow Metab 2004; 24(12): 1317–32.Google Scholar
Galasso, JM, et al. Acute excitotoxic injury induces expression of monocyte chemoattractant protein-1 and its receptor, CCR2, in neonatal rat brain. Exp Neurol 2000; 165(2): 295–305.Google Scholar
Cowell, RM, et al. Hypoxic-ischemic injury induces macrophage inflammatory protein-1alpha expression in immature rat brain. Stroke 2002; 33(3): 795–801.Google Scholar
Cowell, RM, Plane, JM, Silverstein, FS. Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats. J Neurosci 2003; 23(28): 9459–68.Google Scholar
Hu, BR, et al. Involvement of caspase-3 in cell death after hypoxia-ischemia declines during brain maturation. J Cereb Blood Flow Metab 2000; 20(9): 1294–300.Google Scholar
Han, BH, et al. Selective, reversible caspase-3 inhibitor is neuroprotective and reveals distinct pathways of cell death following neonatal hypoxic- ischemic brain injury. J Biol Chem 2002; 277(33): 30128–36.Google Scholar
Yakovlev, AG, et al. Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. J Neurosci 2001; 21(19): 7439–46.Google Scholar
Zhu, C, et al. The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia. Cell Death Differ 2005; 12(2): 162–76.Google Scholar
Manabat, C, et al. Reperfusion differentially induces caspase-3 activation in ischemic core and penumbra after stroke in immature brain. Stroke 2003; 34(1): 207–13.Google Scholar
Bittigau, P, et al. Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain. Ann Neurol 1999; 45(6): 724–35.Google Scholar
Cheng, Y, et al. Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury [see comments]. J Clin Invest 1998; 101(9): 1992–9.Google Scholar
West, T, Atzeva, M, Holtzman, DM. Caspase-3 deficiency during development increases vulnerability to hypoxic-ischemic injury through caspase-3-independent pathways. Neurobiol Dis 2006; 22(3): 523–37.Google Scholar
Zhu, C, et al. X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants. Eur J Neurosci 2007; 26(12): 3402–10.Google Scholar
Matsumori, Y, et al. Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury. J Cereb Blood Flow Metab 2005; 25(7): 899–910.Google Scholar
Blomgren, K, Leist, M, Groc, L. Pathological apoptosis in the developing brain. Apoptosis 2007; 12(5): 993–1010.Google Scholar
Carloni, S, et al. Extended role of necrotic cell death after hypoxia-ischemia-induced neurodegeneration in the neonatal rat. Neurobiol Dis 2007; 27(3): 354–61.Google Scholar
Chavez-Valdez, R, Martin, LJ, Northington, FJ. Programmed necrosis: a prominent mechanism of cell death following neonatal brain injury. Neurol Res Int 2012; 2012: 257563.Google Scholar
Johnston, MV, Hagberg, H. Sex and the pathogenesis of cerebral palsy. Dev Med Child Neurol 2007; 49(1): 74–8.Google Scholar
Zup, SL, Edwards, NS, McCarthy, MM. Sex- and age-dependent effects of androgens on glutamate-induced cell death and intracellular calcium regulation in the developing hippocampus. Neuroscience 2014; 281C: 77–87.Google Scholar
Hagberg, H, et al. PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury. J Neurochem 2004; 90(5)1068–75.Google Scholar
Renolleau, S, Fau, S, Charriaut-Marlangue, C. Gender-related differences in apoptotic pathways after neonatal cerebral ischemia. Neuroscientist 2008; 14(1): 46–52.Google Scholar
Del Pino Sans, J. et al. Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol. Neuroscience 2015; 303: 312–22.Google Scholar
Renolleau, S, et al. Sex, neuroprotection, and neonatal ischemia. Dev Med Child Neurol 2007; 49(6): 477; author reply 477–8.Google Scholar
Nijboer, CH, et al. Gender-specific neuroprotection by 2-iminobiotin after hypoxia-ischemia in the neonatal rat via a nitric oxide independent pathway. J Cereb Blood Flow Metab 2007; 27(2): 282–92.Google Scholar
Nijboer, CH, et al. Gender-dependent pathways of hypoxia-ischemia-induced cell death and neuroprotection in the immature P3 rat. Dev Neurosci 2007; 29(4–5): 385–92.Google Scholar
Wang, GL, Semenza, GL. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem 1993; 268(29): 21513–8.Google Scholar
Bergeron, M, et al. Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur J Neurosci 1999; 11(12): 4159–70.Google Scholar
Chavez, JC, LaManna, JC. Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1. J Neurosci 2002; 22(20): 8922–31.Google Scholar
Bruick, RK, McKnight, SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001; 294(5545): 1337–40.Google Scholar
Semenza, GL. Hypoxia-inducible factor 1: master regulator of O2 homeostasis. Curr Opin Genet Dev 1998; 8(5): 588–94.Google Scholar
Baranova, O, et al. Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci 2007; 27(23): 6320–32.Google Scholar
Zaman, K, et al. Protection from oxidative stress-induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced DNA binding of hypoxia-inducible factor-1 and ATF-1/CREB and increased expression of glycolytic enzymes, p21(waf1/cip1), and erythropoietin. J Neurosci 1999; 19(22): 9821–30.Google Scholar
Bruick, RK. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA 2000; 97(16): 9082–7.Google Scholar
Van Hoecke, M, et al. Evidence of HIF-1 functional binding activity to caspase-3 promoter after photothrombotic cerebral ischemia. Mol Cell Neurosci 2007; 34(1): 40–7.Google Scholar
Helton, R, et al. Brain-specific knock-out of hypoxia-inducible factor-1alpha reduces rather than increases hypoxic-ischemic damage. J Neurosci 2005; 25(16): 4099–107.Google Scholar
Bergeron, M, et al. Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Ann Neurol 2000; 48(3): 285–96.Google Scholar
Mu, D, et al. Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model. Neurobiol Dis 2003; 14(3): 524–34.Google Scholar
Mu, D, et al. Hypoxia-inducible factor 1alpha and erythropoietin upregulation with deferoxamine salvage after neonatal stroke. Exp Neurol 2005; 195(2):407–15.Google Scholar
Li, L, et al. The involvement of phosphoinositid 3-kinase/Akt pathway in the activation of hypoxia-inducible factor-1alpha in the developing rat brain after hypoxia-ischemia. Brain Res 2008; 1197:152–8.Google Scholar
Li, L, et al. The requirement of extracellular signal-related protein kinase pathway in the activation of hypoxia inducible factor 1alpha in the developing rat brain after hypoxia-ischemia. Acta Neuropathol 2008; 115(3): 297–303.Google Scholar
Jones, NM, Bergeron, M. Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat brain. J Cereb Blood Flow Metab 2001; 21(9): 1105–14.Google Scholar
Bernaudin, M, et al. Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. J Biol Chem 2002; 277(42): 39728–38.Google Scholar
Jelkmann, W. Erythropoietin: structure, control of production, and function. Physiol Rev 1992; 72(2): 449–89.Google Scholar
Chen, ZY, et al. Endogenous erythropoietin signaling is required for normal neural progenitor cell proliferation. J Biol Chem 2007; 282(35): 25875–83.Google Scholar
Shingo, T, et al. Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 2001; 21(24): 9733–43.Google Scholar
Wu, H, et al. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 1995; 83(1): 59–67.Google Scholar
Kilic, E, et al. Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB J 2005; 19(14): 2026–8.Google Scholar
Digicaylioglu, M, Lipton, SA. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 2001; 412(6847): 641–7.Google Scholar
Kawakami, M, et al. Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia. J Biol Chem 2001; 276(42): 39469–75.Google Scholar
Marti, HH, et al. Neuroprotection and Angiogenesis: Dual Role of Erythropoietin in Brain Ischemia. News Physiol Sci 2000; 15: 225–9.Google Scholar
Solaroglu, I, et al. Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain. Childs Nerv Syst 2003; 19(1): 19–22.Google Scholar
Sola, A, et al. Potential for protection and repair following injury to the developing brain: a role for erythropoietin? Pediatr Res 2005; 57(5 Pt 2): 110 R–17 R.Google Scholar
Wang, L, et al. Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 2004; 35(7): 1732–7.Google Scholar
Ribatti, D, et al. Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 1999; 93(8): 2627–36.Google Scholar
Sun, Y, Calvert, JW, Zhang, JH. Neonatal hypoxia/ischemia is associated with decreased inflammatory mediators after erythropoietin administration. Stroke 2005; 36(8): 1672–8.Google Scholar
Dzietko, M, et al. Erythropoietin protects the developing brain against N-methyl-D-aspartate receptor antagonist neurotoxicity. Neurobiol Dis 2004; 15(2): 177–87.Google Scholar
Xiong, T, et al. Erythropoietin for neonatal brain injury: opportunity and challenge. Int J Dev Neurosci 2011; 29(6): 583–91.Google Scholar
Kellert, BA, McPherson, RJ, Juul, SE. A comparison of high-dose recombinant erythropoietin treatment regimens in brain-injured neonatal rats. Pediatr Res 2007; 61(4): 451–5.Google Scholar
Spandou, E, et al. Hypoxia-ischemia affects erythropoietin and erythropoietin receptor expression pattern in the neonatal rat brain. Brain Res 2004; 1021(2): 167–72.Google Scholar
McClure, MM, Threlkeld, SW, Fitch, RH. Auditory processing and learning/memory following erythropoietin administration in neonatally hypoxic-ischemic injured rats. Brain Res 2007; 1132(1): 203–9.Google Scholar
Iwai, M, et al. Erythropoietin promotes neuronal replacement through revascularization and neurogenesis after neonatal hypoxia/ischemia in rats. Stroke 2007; 38(10): 2795–803.Google Scholar
Kumral, A, et al. Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats. Behav Brain Res 2004; 153(1): 77–86.Google Scholar
Chang, YS, et al. Erythropoietin improves functional and histological outcome in neonatal stroke. Pediatr Res 2005; 58(1): 106–11.Google Scholar
Gonzalez, F, et al. Erythropoietin enhances long-term neuroprotection and neurogenesis in neonatal stroke. Dev Neurosci 2007; 29(4–5): 321–30.Google Scholar
Gonzalez, FF, et al. Erythropoietin increases neurogenesis and oligodendrogliosis of subventricular zone precursor cells after neonatal stroke. Stroke 2013; 44(3): 753–8.Google Scholar
Zhu, C, et al. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics 2009; 124(2): e218–26.Google Scholar
Elmahdy, H, et al. Human recombinant erythropoietin in asphyxia neonatorum: pilot trial. Pediatrics 2010; 125(5): e1135–42.Google Scholar
Ferrara, N, Gerber, HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001; 106(4): 148–56.Google Scholar
Carmeliet, P, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380(6573): 435–9.Google Scholar
Dougher, M, Terman, BI. Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization. Oncogene 1999; 18(8): 1619–27.Google Scholar
Takahashi, T, et al. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 2001; 20(11): 2768–78.Google Scholar
Fujio, Y, Walsh, K. AKT mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner. J Biol Chem 1999; 274(23): 16349–54.Google Scholar
Shibuya, M. Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1). Int J Biochem Cell Biol 2001; 33(4): 409–20.Google Scholar
Vogel, C, et al. Flt-1, but not Flk-1 mediates hyperpermeability through activation of the PI3-K/Akt pathway. J Cell Physiol 2007; 212(1): 236–43.Google Scholar
Rahimi, N, Dayanir, V, Lashkari, K. Receptor chimeras indicate that the vascular endothelial growth factor receptor-1 (VEGFR-1) modulates mitogenic activity of VEGFR-2 in endothelial cells. J Biol Chem 2000; 275(22): 16986–92.Google Scholar
Autiero, M, et al. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 2003; 9(7): 936–43.Google Scholar
Jin, KL, Mao, XO, Greenberg, DA. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA 2000; 97(18): 10242–7.Google Scholar
Shweiki, D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359(6398): 843–5.Google Scholar
Sun, Y, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 2003; 111(12): 1843–51.Google Scholar
Wang, Y, et al. VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis and neuromigration. J Neurosci Res, 2007. 85(4): p. 740–7.Google Scholar
Zhang, Z.G., et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 2000; 106(7): 829–38.Google Scholar
Manoonkitiwongsa, PS, et al. Neuroprotection of ischemic brain by vascular endothelial growth factor is critically dependent on proper dosage and may be compromised by angiogenesis. J Cereb Blood Flow Metab 2004; 24(6): 693–702.Google Scholar
Ogunshola, OO, et al. Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain. Brain Res Dev Brain Res 2000; 119(1): 139–53.Google Scholar
Laudenbach, V, et al. Neonatal hypoxic preconditioning involves vascular endothelial growth factor. Neurobiol Dis 2007; 26(1): 243–52.Google Scholar
Shimotake, J, et al. Vascular endothelial growth factor receptor-2 inhibition promotes cell death and limits endothelial cell proliferation in a neonatal rodent model of stroke. Stroke 2010; 41(2): 343–9.Google Scholar
Waterhouse, EG, Xu, B. New insights into the role of brain-derived neurotrophic factor in synaptic plasticity. Mol Cell Neurosci 2009; 42(2): 81–9.Google Scholar
Zheng, F, Wang, H. NMDA-mediated and self-induced bdnf exon IV transcriptions are differentially regulated in cultured cortical neurons. Neurochem Int 2009; 54(5–6): 385–92.Google Scholar
Chen, K, et al. Creating a neurogenic environment: the role of BDNF and FGF2. Mol Cell Neurosci 2007; 36(1): 108–20.Google Scholar
Rivera, C, et al. BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl− extrusion. J Cell Biol 2002; 159(5): 747–52.Google Scholar
Gluckman, PD, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365(9460): 663–70.Google Scholar
Shankaran, S, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353(15): 1574–84.Google Scholar
Wyatt, JS, et al. Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics 2007; 119(5): 912–21.Google Scholar
Yager, JY, et al. Preventing hyperthermia decreases brain damage following neonatal hypoxic-ischemic seizures. Brain Res 2004; 1011(1): 48–57.Google Scholar
Mishima, K, et al. Effects of hypothermia and hyperthermia on attentional and spatial learning deficits following neonatal hypoxia-ischemic insult in rats. Behav Brain Res 2004; 151(1–2): 209–17.Google Scholar
Zhu, C, et al. Post-ischemic hypothermia-induced tissue protection and diminished apoptosis after neonatal cerebral hypoxia-ischemia. Brain Res 2004; 996(1): 67–75.Google Scholar
Wagner, BP, Nedelcu, J, Martin, E. Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats. Pediatr Res 2002; 51(3): 354–60.Google Scholar
Liu, Y, et al. Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats. Stroke 2004; 35(6): 1460–5.Google Scholar
Thoresen, M, et al. A piglet survival model of posthypoxic encephalopathy. Pediatr Res 1996; 40(5): 738–48.Google Scholar
Bona, E, et al. Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short- and long-term outcome. Pediatr Res 1998; 43(6): 738–45.Google Scholar
Taylor, DL, et al. Improved neuroprotection with hypothermia delayed by 6 hours following cerebral hypoxia-ischemia in the 14-day-old rat. Pediatr Res 2002; 51(1): 13–9.Google Scholar
Gunn, AJ, et al. Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J Clin Invest 1997; 99(2): 248–56.Google Scholar
Gunn, AJ, et al. Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep. Pediatr Res 1999; 46(3): 274–80.Google Scholar
Jatana, M, et al. Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res 2006; 59(5): 684–9.Google Scholar
Hobbs, CT, Tucker, M, Aquilina, A, et al. Xenon and hypothermia combine additively. offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke 2008; 39(4):1307–13.Google Scholar
Wu, YW, et al. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics 2012; 130(4): 683–91.Google Scholar
Loren, DJ, et al. Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. Pediatr Res 2005; 57(6): 858–64.Google Scholar
West, T, Atzeva, M, Holtzman, DM. Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury. Dev Neurosci 2007; 29(4–5): 363–72.Google Scholar
Feng, Y, et al. Grape seed extract given three hours after injury suppresses lipid peroxidation and reduces hypoxic-ischemic brain injury in neonatal rats. Pediatr Res 2007; 61(3): 295–300.Google Scholar
Parent, JM, et al. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002; 52(6): 802–13.Google Scholar
Lindvall, O, Kokaia, Z. Recovery and rehabilitation in stroke: stem cells. Stroke 2004; 35(11 Suppl. 1): 2691–4.Google Scholar
Plane, JM, et al. Neonatal hypoxic-ischemic injury increases forebrain subventricular zone neurogenesis in the mouse. Neurobiol Dis 2004; 16(3): 585–95.Google Scholar
Arvidsson, A, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8(9): 963–70.Google Scholar
Zhang, R, et al. Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J Cereb Blood Flow Metab 2004; 24(4): 441–8.Google Scholar
Zhang, R, et al. Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat. J Neurosci 2004; 24(25): 5810–5.Google Scholar
Ohab, JJ, et al. A neurovascular niche for neurogenesis after stroke. J Neurosci 2006; 26(50): 13007–16.Google Scholar
Romanko, MJ, et al. Death effector activation in the subventricular zone subsequent to perinatal hypoxia/ischemia. J Neurochem 2007; 103(3): 1121–31.Google Scholar
Yang, Z, et al. Sustained neocortical neurogenesis after neonatal hypoxic/ischemic injury. Ann Neurol 2007; 61(3): 199–208.Google Scholar
Greenberg, DA, Jin, K. From angiogenesis to neuropathology. Nature 2005; 438(7070): 954–9.Google Scholar
Distler, JH, et al. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 2003; 47(3): 149–61.Google Scholar
van Velthoven, CT, Kavelaars, A, Heijnen, CJ. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage. Pediatr Res 2012; 71(4 Pt 2): 474–81.Google Scholar
van Velthoven, CT, et al. Stem cells for neonatal stroke: the future is here. Front Cell Neurosci 2014; 8: 207.Google Scholar

References

Wilson-Costello, D, Friedman, H, Minich, N, et al. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics 2005; 115: 997–1003.Google Scholar
Moore, T, Hennessy, EM, Myles, J, et al. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ (Clinical Research Edition) 2012; 345: e7961.Google Scholar
Schlapbach, LJ, Adams, M, Proietti, E, et al. Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008. BMC Pediatrics 2012; 12: 198.Google Scholar
Hintz, SR, Kendrick, DE, Wilson-Costello, DE, et al. Early-childhood neurodevelopmental outcomes are not improving for infants born at <25 weeks’ gestational age. Pediatrics 2011; 127: 62–70.Google Scholar
Wilson-Costello, D, Friedman, H, Minich, N, et al. Improved neurodevelopmental outcomes for extremely low birth weight infants in 2000–2002. Pediatrics 2007; 119: 37–45.Google Scholar
Hack, M. Young adult outcomes of very-low-birth-weight children. Semin Fetal Neonatal Med 2006; 11: 127–37.Google Scholar
Baron, IS, Erickson, K, Ahronovich, MD, et al. Cognitive deficit in preschoolers born late preterm. Early Hum Dev. 2011; 87: 115–9.Google Scholar
Committee on Understanding Premature Birth and Assuring Healthy Outcomes, Behrman, RE, Butler, AS, eds. Preterm Birth: Causes, Consequences, and Prevention. Washington, DC: Institute of Medicine of the National Academies, 2007. Available from http://books.nap.edu/openbook.php?record_id=11622&page=1.Google Scholar
Saigal, S, Doyle, LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet 2008; 371: 261–9.Google Scholar
Perlman, JM. White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome. Early Hum Dev 1998; 53: 99–120.Google Scholar
Andiman, SE, Haynes, RL, Trachtenberg, FL, et al. The cerebral cortex overlying periventricular leukomalacia: analysis of pyramidal neurons. Brain Pathol 2010; 20: 803–14.Google Scholar
Reid, SM, Ditchfield, MR, Bracken, J, Reddihough, DS. Relationship between characteristics on magnetic resonance imaging and motor outcomes in children with cerebral palsy and white matter injury. Res Dev Disabil 2015; 45–6: 178–87.Google Scholar
Okumura, A, Kato, T, Kuno, K, et al. MRI findings in patients with spastic cerebral palsy. II. Correlation with type of cerebral palsy. Dev Med Child Neurol 1997; 39: 369–72.Google Scholar
Hamrick, SE, Miller, SP, Leonard, C, et al. Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia. J Pediatr 2004; 145: 593–9.Google Scholar
Buser, JR, Maire, J, Riddle, A, et al. Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants. Ann Neurol 2012; 71: 93–109.Google Scholar
Gano, D, Andersen, SK, Partridge, JC, et al. Diminished white matter injury over time in a cohort of premature newborns. J Pediatr 2015; 166: 39–43.Google Scholar
Haynes, RL, Billiards, SS, Borenstein, NS, et al. Diffuse axonal injury in periventricular leukomalacia as determined by apoptotic marker fractin. Pediatr Res 2008; 63: 656–61.Google Scholar
Riddle, A, Dean, J, Buser, JR, et al. Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury. Ann Neurol 2011; 70: 493–507.Google Scholar
Riddle, A, Maire, J, Gong, X, et al. Differential susceptibility to axonopathy in necrotic and non-necrotic perinatal white matter injury. Stroke 2012; 43: 178–84.Google Scholar
Back, SA, Luo, NL, Mallinson, RA, et al. Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes. Ann Neurol 2005; 58: 108–20.Google Scholar
Segovia, KN, McClure, M, Moravec, M, et al. Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury. Ann Neurol 2008; 63: 520–30.Google Scholar
Franklin, RJ, Gallo, V. The translational biology of remyelination: past, present, and future. Glia 2014; 62: 1905–15.Google Scholar
Billiards, SS, Haynes, RL, Folkerth, RD, et al. Myelin abnormalities without oligodendrocyte loss in periventricular leukomalacia. Brain Pathol 2008; 18: 153–63.Google Scholar
Verney, C, Pogledic, I, Biran, V, et al. Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants. J Neuropathol Exp Neurol 2012; 71: 251–64.Google Scholar
Davidson, JO, Drury, PP, Green, CR, et al. Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep. PLoS One 2014; 9: e96558.Google Scholar
Ritter, J, Schmitz, T, Chew, LJ, et al. Neonatal hyperoxia exposure disrupts axon-oligodendrocyte integrity in the subcortical white matter. J Neurosci 2013; 33: 8990–9002.Google Scholar
Jablonska, B, Scafidi, J, Aguirre, A, et al. Oligodendrocyte regeneration after neonatal hypoxia requires Fox O1-mediated p27Kip1 expression. J Neurosci 2012; 32: 14775–93.Google Scholar
Yuen, TJ, Silbereis, JC, Griveau, A, et al. Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis. Cell 2014; 158: 383–96.Google Scholar
Tolcos, M, Bateman, E, O’Dowd, R, et al. Intrauterine growth restriction affects the maturation of myelin. Exp Neurol 2011; 232: 53–65.Google Scholar
Brehmer, F, Bendix, I, Prager, S, et al. Interaction of inflammation and hyperoxia in a rat model of neonatal white matter damage. PloS One 2012; 7: e49023.Google Scholar
Favrais, G, van de Looij, Y, Fleiss, B, et al. Systemic inflammation disrupts the developmental program of white matter. Ann Neurol 2011; 70: 550–65.Google Scholar
Nobuta, H, Ghiani, CA, Paez, PM, et al. STAT3-mediated astrogliosis protects myelin development in neonatal brain injury. Ann Neurol 2012; 72: 750–65.Google Scholar
Woodward, LJ, Anderson, PJ, Austin, NC, et al. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 2006; 355: 685–94.Google Scholar
Miller, SP, Ferriero, DM, Leonard, C, et al. Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr 2005; 147: 609–16.Google Scholar
Pierson, CR, Folkerth, RD, Billiards, SS, et al. Gray matter injury associated with periventricular leukomalacia in the premature infant. Acta Neuropathol 2007; 114: 619–31.Google Scholar
Lin, Y, Okumura, A, Hayakawa, F, et al. Quantitative evaluation of thalami and basal ganglia in infants with periventricular leukomalacia. Dev Med Child Neurol 2001; 43: 481–5.Google Scholar
Peterson, BS, Vohr, B, Staib, LH, et al. Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. JAMA 2000; 284: 1939–47.Google Scholar
Counsell, SJ, Dyet, LE, Larkman, DJ, et al. Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography. Neuroimage 2007; 34: 896–904.Google Scholar
Ball, G, Boardman, JP, Rueckert, D, et al. The effect of preterm birth on thalamic and cortical development. Cereb Cortex 2012; 22: 1016–24.Google Scholar
Smyser, CD, Snyder, AZ, Shimony, JS, et al. Effects of white matter injury on resting state fMRI measures in prematurely born infants. PloS One 2013; 8: e68098.Google Scholar
Pitcher, JB, Riley, AM, Doeltgen, SH, et al. Physiological evidence consistent with reduced neuroplasticity in human adolescents born preterm. J Neurosci 2012; 32: 16410–6.Google Scholar
Pitcher, JB, Schneider, LA, Burns, NR, et al. Reduced corticomotor excitability and motor skills development in children born preterm. J Physiol 2012; 590: 5827–44.Google Scholar
Ajayi-Obe, M, Saeed, N, Cowan, FM, et al. Reduced development of cerebral cortex in extremely preterm infants. Lancet 2000; 356: 1162–3.Google Scholar
Nosarti, C, Al-Asady, MH, Frangou, S, et al. Adolescents who were born very preterm have decreased brain volumes. Brain 2002; 125: 1616–23.Google Scholar
Martinussen, M, Fischl, B, Larsson, HB, et al. Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method. Brain 2005; 128: 2588–96.Google Scholar
Isaacs, EB, Edmonds, CJ, Chong, WK, et al. Brain morphometry and IQ measurements in preterm children. Brain 2004; 127: 2595–607.Google Scholar
Abernethy, LJ, Cooke, RW, Foulder-Hughes, L. Caudate and hippocampal volumes, intelligence, and motor impairment in 7-year-old children who were born preterm. Pediatr Res 2004; 55: 884–93.Google Scholar
Gimenez, M, Junque, C, Narberhaus, A, et al. Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity. Neuroimage 2004; 23: 869–77.Google Scholar
Felderhoff-Mueser, U, Rutherford, MA, Squier, WV, et al. Relationship between MR imaging and histopathologic findings of the brain in extremely sick preterm infants. AJNR Am J Neuroradiol 1999; 20: 1349–57.Google Scholar
Takizawa, Y, Takashima, S, Itoh, M. A histopathological study of premature and mature infants with pontosubicular neuron necrosis: neuronal cell death in perinatal brain damage. Brain Res 2006; 1095: 200–6.Google Scholar
Bell, JE, Becher, JC, Wyatt, B, et al. Brain damage and axonal injury in a Scottish cohort of neonatal deaths. Brain 2005; 128: 1070–81.Google Scholar
Barkovich, AJ, Sargent, SK. Profound asphyxia in the premature infant: imaging findings. AJNR Am J Neuroradiol 1995; 16: 1837–46.Google Scholar
Geddes, R, Vannucci, RC, Vannucci, SJ. Delayed cerebral atrophy following moderate hypoxia-ischemia in the immature rat. Dev Neurosci 2001; 23: 180–5.Google Scholar
Goldberg, JL, Barres, BA. The relationship between neuronal survival and regeneration. Annu Rev Neurosci 2000; 23: 579–612.Google Scholar
Jacobson, MD, Weil, M, Raff, MC. Programmed cell death in animal development. Cell 1997; 88: 347–54.Google Scholar
Meng, SZ, Arai, Y, Deguchi, K, Takashima, S. Early detection of axonal and neuronal lesions in prenatal-onset periventricular leukomalacia. Brain Dev 1997; 19: 480–4.Google Scholar
Hirayama, A, Okoshi, Y, Hachiya, Y, et al. Early immunohistochemical detection of axonal damage and glial activation in extremely immature brains with periventricular leukomalacia. Clin Neuropathol 2001; 20: 87–91.Google Scholar
de Graaf-Peters, VB, Hadders-Algra, M. Ontogeny of the human central nervous system: what is happening when? Early Hum Dev 2006; 82: 257–66.Google Scholar
Dean, JM, McClendon, E, Hansen, K, et al. Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization. Sci Transl Med 2013; 5: 168ra7.Google Scholar
Sizonenko, SV, Camm, EJ, Garbow, JR, et al. Developmental changes and injury induced disruption of the radial organization of the cortex in the immature rat brain revealed by in vivo diffusion tensor MRI. Cereb Cortex 2007; 17: 2609–17.Google Scholar
Back, SA, Riddle, A, Dean, J, Hohimer, AR. The instrumented fetal sheep as a model of cerebral white matter injury in the premature infant. Neurotherapeutics 2012; 9: 359–70.Google Scholar
Vinall, J, Grunau, RE, Brant, R, et al. Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns. Sci Transl Med 2013; 5: 168ra8.Google Scholar
Ball, G, Srinivasan, L, Aljabar, P, et al. Development of cortical microstructure in the preterm human brain. Proc Natl Acad Sci USA 2013; 110: 9541–6.Google Scholar
Constable, RT, Ment, LR, Vohr, BR, et al. Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects. Pediatrics 2008; 121: 306–16.Google Scholar
de Vries, LS, Eken, P, Groenendaal, F, et al. Antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants: prevalence and associated obstetric variables. Arch Dis Child Fetal Neonatal Ed 1998; 78: F51–6.Google Scholar
Hayakawa, F, Okumura, A, Kato, T, et al. Determination of timing of brain injury in preterm infants with periventricular leukomalacia with serial neonatal electroencephalography. Pediatrics 1999; 104: 1077–81.Google Scholar
Becher, JC, Bell, JE, Keeling, JW, et al. The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths. Arch Dis Child Fetal Neonatal Ed 2004; 89: F399–407.Google Scholar
Kubota, T, Okumura, A, Hayakawa, F, et al. Combination of neonatal electroencephalography and ultrasonography: sensitive means of early diagnosis of periventricular leukomalacia. Brain Dev 2002; 24: 698–702.Google Scholar
Weinberger, B, Anwar, M, Hegyi, T, et al. Antecedents and neonatal consequences of low Apgar scores in preterm newborns: a population study. Arch Pediatr Adolesc Med 2000; 154: 294–300.Google Scholar
Osborn, DA, Evans, N, Kluckow, M. Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics 2003; 112: 33–9.Google Scholar
Low, JA. Determining the contribution of asphyxia to brain damage in the neonate. J Obstet Gynaecol Res 2004; 30: 276–86.Google Scholar
Salhab, WA, Perlman, JM. Severe fetal acidemia and subsequent neonatal encephalopathy in the larger premature infant. Pediatr Neurol 2005; 32: 25–9.Google Scholar
George, S, Gunn, AJ, Westgate, JA, et al. Fetal heart rate variability and brainstem injury after asphyxia in preterm fetal sheep. Am J Physiol Regul Integr Comp Physiol 2004; 287: R925–33.Google Scholar
Dean, JM, George, SA, Wassink, G, et al. Suppression of post hypoxic-ischemic EEG transients with dizocilpine is associated with partial striatal protection in the preterm fetal sheep. Neuropharmacology 2006; 50: 491–503.Google Scholar
Dean, JM, Gunn, AJ, Wassink, G, et al. Endogenous alpha[2]-adrenergic receptor-mediated neuroprotection after severe hypoxia in preterm fetal sheep. Neuroscience 2006; 142: 615–28.Google Scholar
Bennet, L, Roelfsema, V, George, S, et al. The effect of cerebral hypothermia on white and gray matter injury induced by severe hypoxia in preterm fetal sheep. J Physiol 2007; 578: 491–506.Google Scholar
Gunn, AJ, Quaedackers, JS, Guan, J, et al. The premature fetus: not as defenseless as we thought, but still paradoxically vulnerable? Dev Neurosci 2001; 23: 175–9.Google Scholar
Volpe, JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res 2001; 50: 553–62.Google Scholar
Riddle, A, Luo, NL, Manese, M, et al. Spatial heterogeneity in oligodendrocyte lineage maturation and not cerebral blood flow predicts fetal ovine periventricular white matter injury. J Neurosci 2006; 26: 3045–55.Google Scholar
Osborn, DA, Evans, N, Kluckow, M. Clinical detection of low upper body blood flow in very premature infants using blood pressure, capillary refill time, and central-peripheral temperature difference. Arch Dis Child Fetal Neonatal Ed 2004; 89: F168–73.Google Scholar
Kluckow, M, Evans, N. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed 2000; 82: F182–7.Google Scholar
Meek, JH, Elwell, CE, McCormick, DC, et al. Abnormal cerebral haemodynamics in perinatally asphyxiated neonates related to outcome. Arch Dis Child Fetal Neonatal Ed 1999; 81: F110–15.Google Scholar
Hunt, RW, Evans, N, Rieger, I, Kluckow, M. Low superior vena cava flow and neurodevelopment at 3 years in very preterm infants. J Pediatr 2004; 145: 588–92.Google Scholar
Lou, HC, Lassen, NA, Tweed, WA, et al. Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia. Acta Paediatr Scand 1979; 68: 57–63.Google Scholar
Soul, JS, Hammer, PE, Tsuji, M, et al. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res 2007; 61: 467–73.Google Scholar
Martens, SE, Rijken, M, Stoelhorst, GM, et al. Is hypotension a major risk factor for neurological morbidity at term age in very preterm infants? Early Hum Dev 2003; 75: 79–89.Google Scholar
Murphy, DJ, Hope, PL, Johnson, A. Neonatal risk factors for cerebral palsy in very preterm babies: case-control study. BMJ 1997; 314: 404–8.Google Scholar
Low, JA, Froese, AB, Galbraith, RS, et al. The association between preterm newborn hypotension and hypoxemia and outcome during the first year. Acta Paediatr 1993; 82: 433–7.Google Scholar
Trounce, JQ, Shaw, DE, Levene, MI, Rutter, N. Clinical risk factors and periventricular leucomalacia. Arch Dis Child. 1988; 63: 17–22.Google Scholar
Perlman, JM, Risser, R, Broyles, RS. Bilateral cystic periventricular leukomalacia in the premature infant: associated risk factors. Pediatrics 1996; 97: 822–7.Google Scholar
Dammann, O, Allred, EN, Kuban, KC, et al. Systemic hypotension and white-matter damage in preterm infants. Dev Med Child Neurol 2002; 44: 82–90.Google Scholar
Cunningham, S, Symon, AG, Elton, RA, et al. Intra-arterial blood pressure reference ranges, death and morbidity in very low birth weight infants during the first seven days of life. Early Hum Dev 1999; 56: 151–65.Google Scholar
Limperopoulos, C, Bassan, H, Kalish, LA, et al. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics 2007; 120: 966–77.Google Scholar
Bennet, L, Booth, L, Malpas, SC, et al. Acute systemic complications in the preterm fetus after asphyxia: the role of cardiovascular and blood flow responses. Clin Exp Pharmacol Physiol 2006; 33: 291–9.Google Scholar
Osborn, DA. Diagnosis and treatment of preterm transitional circulatory compromise. Early Hum Dev 2005; 81: 413–22.Google Scholar
Tan, WK, Williams, CE, During, MJ, et al. Accumulation of cytotoxins during the development of seizures and edema after hypoxic-ischemic injury in late gestation fetal sheep. Pediatr Res 1996; 39: 791–7.Google Scholar
Choi, DW. Excitotoxic cell death. J Neurobiol 1992; 23: 1261–76.Google Scholar
Mitani, A, Andou, Y, Kataoka, K. Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil: brain microdialysis study. Neuroscience 1992; 48: 307–13.Google Scholar
McDonald, JW, Johnston, MV, Young, AB. Differential ontogenic development of three receptors comprising the NMDA receptor/channel complex in the rat hippocampus. Exp Neurol 1990; 110: 237–47.Google Scholar
Fern, R, Moller, T. Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci 2000; 20: 34–42.Google Scholar
Follett, PL, Rosenberg, PA, Volpe, JJ, Jensen, FE. NBQX attenuates excitotoxic injury in developing white matter. J Neurosci 2000; 20: 9235–41.Google Scholar
Rossi, DJ, Oshima, T, Attwell, D. Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 2000; 403: 316–21.Google Scholar
Desilva, TM, Kinney, HC, Borenstein, NS, et al. The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter. J Comp Neurol 2007; 501: 879–90.Google Scholar
Dean, JM, Fraser, M, Shelling, AN, et al. Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white matter and cerebral cortex. Brain Res Mol Brain Res 2005; 139: 242–50.Google Scholar
Itoh, T, Beesley, J, Itoh, A, et al. AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes. J Neurochem 2002; 81: 390–402.Google Scholar
Follett, PL, Deng, W, Dai, W, et al. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J Neurosci 2004; 24: 4412–20.Google Scholar
Back, SA, Riddle, A, McClure, MM. Maturation-dependent vulnerability of perinatal white matter in premature birth. Stroke 2007; 38: 724–30.Google Scholar
Fraser, M, Bennet, L, van Zijl, PL, et al. Extracellular amino acids and peroxidation products in the periventricular white matter during and after cerebral ischemia in preterm fetal sheep. J Neurochem 2008; 105: 2214–23.Google Scholar
Fraser, M, Bennet, L, Gunning, M, et al. Cortical electroencephalogram suppression is associated with post-ischemic cortical injury in 0.65 gestation fetal sheep. Brain Res Dev Brain Res 2005; 154: 45–55.Google Scholar
Dohmen, C, Kumura, E, Rosner, G, et al. Extracellular correlates of glutamate toxicity in short-term cerebral ischemia and reperfusion: a direct in vivo comparison between white and gray matter. Brain Res 2005; 1037: 43–51.Google Scholar
Henderson, JL, Reynolds, JD, Dexter, F, et al. Chronic hypoxemia causes extracellular glutamate concentration to increase in the cerebral cortex of the near-term fetal sheep. Brain Res Dev Brain Res 1998; 105: 287–93.Google Scholar
Loeliger, M, Watson, CS, Reynolds, JD, et al. Extracellular glutamate levels and neuropathology in cerebral white matter following repeated umbilical cord occlusion in the near term fetal sheep. Neuroscience 2003; 116: 705–14.Google Scholar
Kumura, E, Graf, R, Dohmen, C, et al. Breakdown of calcium homeostasis in relation to tissue depolarization: comparison between gray and white matter ischemia. J Cereb Blood Flow Metab 1999; 19: 788–93.Google Scholar
Back, SA, Gan, X, Li, Y, et al. Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci 1998; 18: 6241–53.Google Scholar
Rosin, C, Bates, TE, Skaper, SD. Excitatory amino acid induced oligodendrocyte cell death in vitro: receptor-dependent and -independent mechanisms. J Neurochem 2004; 90: 1173–85.Google Scholar
Inder, T, Mocatta, T, Darlow, B, et al. Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury. Pediatr Res 2002; 52: 213–8.Google Scholar
Haynes, RL, Folkerth, RD, Keefe, RJ, et al. Nitrosative and oxidative injury to premyelinating oligodendrocytes in periventricular leukomalacia. J Neuropathol Exp Neurol 2003; 62: 441–50.Google Scholar
Welin, AK, Sandberg, M, Lindblom, A, et al. White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain. Pediatr Res 2005; 58: 100–5.Google Scholar
Deng, W, Rosenberg, PA, Volpe, JJ, Jensen, FE. Calcium-permeable AMPA/kainate receptors mediate toxicity and preconditioning by oxygen-glucose deprivation in oligodendrocyte precursors. Proc Natl Acad Sci USA 2003; 100: 6801–6.Google Scholar
Willoughby, RE Jr., Nelson, KB. Chorioamnionitis and brain injury. Clin Perinatol 2002; 29: 603–21.Google Scholar
Wang, X, Rousset, CI, Hagberg, H, Mallard, C. Lipopolysaccharide-induced inflammation and perinatal brain injury. Semin Fetal Neonatal Med 2006; 11: 343–53.Google Scholar
Yoon, BH, Park, CW, Chaiworapongsa, T. Intrauterine infection and the development of cerebral palsy. BJOG 2003; 110: 124–7.Google Scholar
Holcroft, CJ, Blakemore, KJ, Allen, M, Graham, EM. Association of prematurity and neonatal infection with neurologic morbidity in very low birth weight infants. Obstet Gynecol 2003; 101: 1249–53.Google Scholar
Ellison, VJ, Mocatta, TJ, Winterbourn, CC, et al. The relationship of CSF and plasma cytokine levels to cerebral white matter injury in the premature newborn. Pediatr Res 2005; 57: 282–6.Google Scholar
Duggan, PJ, Maalouf, EF, Watts, TL, et al. Intrauterine T-cell activation and increased proinflammatory cytokine concentrations in preterm infants with cerebral lesions. Lancet 2001; 358: 1699–700.Google Scholar
Kadhim, H, Tabarki, B, Verellen, G, et al. Inflammatory cytokines in the pathogenesis of periventricular leukomalacia. Neurology 2001; 56: 1278–84.Google Scholar
Flenady, V, Hawley, G, Stock, OM, et al. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database of Systematic Reviews 2013; 12: CD000246.Google Scholar
Keogh, MJ, Bennet, L, Drury, PP, et al. Subclinical exposure to low-dose endotoxin impairs EEG maturation in preterm fetal sheep. Am J Physiol Regul Integr Comp Physiol 2012; 303: R270–8.Google Scholar
Dean, JM, van de Looij, Y, Sizonenko, SV, et al. Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep. Ann Neurol 2011; 70: 846–56.Google Scholar
Mathai, S, Booth, LC, Davidson, JO, et al. Acute on chronic exposure to endotoxin in preterm fetal sheep. Am J Physiol Regul Integr Comp Physiol 2013; 304: R189–97.Google Scholar
Hellstrom, IC, Danik, M, Luheshi, GN, Williams, S. Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-β-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons. Hippocampus 2005; 15: 656–64.Google Scholar
Luk, WP, Zhang, Y, White, TD, et al. Adenosine: a mediator of interleukin-1beta-induced hippocampal synaptic inhibition. J Neurosci 1999; 19: 4238–44.Google Scholar
Summers deLuca, L, Gommerman, JL. Fine-tuning of dendritic cell biology by the TNF superfamily. Nat Rev Immunol 2012; 12: 339–51.Google Scholar
Kim, IJ, Beck, HN, Lein, PJ, Higgins, D. Interferon gamma induces retrograde dendritic retraction and inhibits synapse formation. J Neurosci 2002; 22: 4530–9.Google Scholar
Duncan, JR, Cock, ML, Scheerlinck, JP, et al. White matter injury after repeated endotoxin exposure in the preterm ovine fetus. Pediatr Res 2002; 52: 941–9.Google Scholar
Nitsos, I, Rees, SM, Duncan, J, et al. Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain. J Soc Gynecol Invest 2006; 13: 239–47.Google Scholar
Duncan, JR, Cock, ML, Suzuki, K, et al. Chronic endotoxin exposure causes brain injury in the ovine fetus in the absence of hypoxemia. J Soc Gynecol Invest 2006; 13: 87–96.Google Scholar
Dommergues, MA, Patkai, J, Renauld, JC, et al. Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium. Ann Neurol 2000; 47: 54–63.Google Scholar
Basu, A, Lazovic, J, Krady, JK, et al. Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury. J Cereb Blood Flow Metab 2005; 25: 17–29.Google Scholar
Loddick, SA, Wong, ML, Bongiorno, PB, et al. Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochem Biophys Res Commun 1997; 234: 211–5.Google Scholar
Kremlev, SG, Palmer, C. Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures. J Neuroimmunol 2005; 162: 71–80.Google Scholar
Loddick, SA, Turnbull, AV, Rothwell, NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1998; 18: 176–9.Google Scholar
Guan, J, Miller, OT, Waugh, KM, et al. TGF-β1 and neurological function after hypoxia-ischemia in adult rats. Neuroreport 2004; 15: 961–4.Google Scholar
Spera, PA, Ellison, JA, Feuerstein, GZ, Barone, FC. IL-10 reduces rat brain injury following focal stroke. Neurosci Lett 1998; 251: 189–92.Google Scholar
Back, SA, Luo, NL, Borenstein, NS, et al. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci 2001; 21: 1302–12.Google Scholar
Cai, Z, Lin, S, Pang, Y, Rhodes, PG. Brain injury induced by intracerebral injection of interleukin-1β and tumor necrosis factor α in the neonatal rat. Pediatr Res 2004; 56: 377–84.Google Scholar
Allan, SM, Rothwell, NJ. Inflammation in central nervous system injury. Philos Trans R Soc Lond B 2003; 358: 1669–77.Google Scholar
Woiciechowsky, C, Schoning, B, Stoltenburg-Didinger, G, et al. Brain-IL-1β triggers astrogliosis through induction of IL-6: inhibition by propranolol and IL-10. Med Sci Monit 2004; 10:BR325–30.Google Scholar
Bal-Price, A, Brown, GC. Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci 2001; 21: 6480–91.Google Scholar
van den Tweel, ER, Nijboer, C, Kavelaars, A, et al. Expression of nitric oxide synthase isoforms and nitrotyrosine formation after hypoxia-ischemia in the neonatal rat brain. J Neuroimmunol 2005; 167: 64–71.Google Scholar
Raivich, G, Bohatschek, M, Kloss, CU, et al. Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Res Rev 1999; 30: 77–105.Google Scholar
Rock, RB, Gekker, G, Hu, S, et al. Role of microglia in central nervous system infections. Clin Microbiol Rev 2004; 17: 942–64.Google Scholar
Pang, Y, Cai, Z, Rhodes, PG. Effects of lipopolysaccharide on oligodendrocyte progenitor cells are mediated by astrocytes and microglia. J Neurosci Res 2000; 62: 510–20.Google Scholar
Yan, E, Castillo-Melendez, M, Nicholls, T, Hirst, J, Walker, D. Cerebrovascular responses in the fetal sheep brain to low-dose endotoxin. Pediatr Res 2004; 55: 855–63.Google Scholar
Folkerth, RD, Keefe, RJ, Haynes, RL, et al. Interferon-gamma expression in periventricular leukomalacia in the human brain. Brain Pathol 2004; 14: 265–74.Google Scholar
Tahraoui, SL, Marret, S, Bodenant, C, et al. Central role of microglia in neonatal excitotoxic lesions of the murine periventricular white matter. Brain Pathol 2001; 11: 56–71.Google Scholar
Kinney, HC. Human myelination and perinatal white matter disorders. J Neurol Sci 2005; 228: 190–2.Google Scholar
Fan, LW, Pang, Y, Lin, S, et al. Minocycline attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain. Neuroscience 2005; 133: 159–68.Google Scholar
Pang, Y, Rodts-Palenik, S, Cai, Z, et al. Suppression of glial activation is involved in the protection of IL-10 on maternal E. coli-induced neonatal white matter injury. Brain Res Dev Brain Res 2005; 157: 141–9.Google Scholar
Gunn, AJ, Bennet, L. Is temperature important in delivery room resuscitation? Semin Neonatol 2001; 6: 241–9.Google Scholar
Yoneyama, Y, Sawa, R, Kubonoya, K, et al. Evidence for mechanisms of the acute-phase response to endotoxin in late-gestation fetal goats. Am J Obstet Gynecol 1998; 179: 750–5.Google Scholar
Mallard, C, Welin, AK, Peebles, D, et al. White matter injury following systemic endotoxemia or asphyxia in the fetal sheep. Neurochem Res 2003; 28: 215–23.Google Scholar
Peebles, DM, Miller, S, Newman, JP, et al. The effect of systemic administration of lipopolysaccharide on cerebral haemodynamics and oxygenation in the 0.65 gestation ovine fetus in utero. BJOG 2003; 110: 735–43.Google Scholar
Nitsos, I, Moss, TJ, Cock, ML, et al. Fetal responses to intra-amniotic endotoxin in sheep. J Soc Gynecol Invest 2002; 9: 80–5.Google Scholar
Dean, JM, Bennet, L, Back, SA, et al. What brakes the preterm brain? An arresting story. Pediatr Res 2014; 75: 227–33.Google Scholar

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