Abstract
Cerebral palsy (CP) is a group of disorders of movement and posture resulting from non-progressive disturbances of the fetal or neonatal brain. More than 80% of cases of CP in term infants originate in the prenatal period; in premature infants, both prenatal or postnatal causes contribute. The most prevalent pathological lesion seen in CP is periventricular white matter injury (PWMI) resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32 wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a spectrum of cognitive and behavioral disorders. Oxidative stress and excitotoxicity resulting from excessive stimulation of ionotropic glutamate receptors on preOLs are the most prominent molecular mechanisms for PWMI. Asphyxia around the time of birth in term infants accounts for less than 15% of CP in developed countries but the incidence is higher in underdeveloped areas Asphyxia causes a different pattern of brain injury and CP than is seen after preterm injuries. This type of CP is associated with the clinical syndrome of hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal ganglia, and brainstem are selectively vulnerable to injury. Experimental models indicate that neurons in the neonatal brain are more likely to die by delayed apoptosis extending over days to weeks than those in the adult brain. Neurons die by glutamate-mediated excitotoxicity involving downstream caspase-dependent and caspase-independent cell death pathways. Recent reports indicate that males and females preferentially utilize different pathways. Clinical trials indicate that mild hypothermia reduces death or disability in term infants following asphyxia and basic research suggests that this approach might be combined with pharmacological strategies in the future.
Similar content being viewed by others
References
Accardo J., Kammann H., and Hoon A. H. Jr. (2004) Neuroimaging in cerebral palsy. J. Pediatr. 145, S19-S27.
Back S. A. and Rivkees S. A. (2004) Emerging concepts in periventricular white matter injury. Semin. Perinatol. 28, 405–414.
Back S. A., Luo N. L., Borenstein N. S., Levine J. M., Volpe J. J., and Kinney H. C. (2001) Late oligodendrocyte progenitors conincide with the developmental window of vulnerability for human perinatal white matter injury. J. Neurosci. 21, 1302–1312.
Back S. A., Luo N. L., Mallinson R. A., et al. (2005) Selective vulnerability of preterm white matter to oxidative damage defined by F2-isoprostanes. Ann. Neurol. 58, 108–120.
Badawi N., Kurinczuk J. J., and Keogh J. M. (1998) Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ. 317, 1554–1558.
Banker B. Q. and Larroche J. C. (1962) Periventricular leukomalacia of infancy. pp. 386–410.
Bano D., Young K. W., Guerin C. J., et al. (2005) Cleavage of the plasma membrane NA+/Ca+ exchanger in excitotoxicity. Cell. 120, 275–285.
Barkovich A. J., Westmark K., Partridge C., Sola A., and Ferriero D. M. (1995) Perinatal asphyxia: MR findings in the first 10 days. AJNR Am. J. Neuroradiol. 16, 427–438.
Baud O., Li J., Zhang Y., Neve R. L., Volpe J. J., and Rosenberg P. A. (2004) Nitric oxide-induced cell death in developing oligodendrocytes is associated with mitochondrial dysfunction and apoptosis-inducing factor translocation. Eur. J. Neurosci. 20, 1713–1726.
Bax M., Goldstein M., Rosenbaum P., et al. (2005) Proposed definition and classification of cerebral palsy, April 2005. Dev. Med. Child. Neurol. 47, 571–576.
Bergles D. E., Roberts J. D., Somogyi P., and Jahr C. E. (2000) Glutamatergic synapses on oligodendrocyte precursor cells in hippocampus. Nature. 405, 187–191.
Blomgren K., Zhu C., Hallin U., and Hagberg H. (2003) Mitochondria and ischemic reperfusion damage in the adult and in the developing brain. Biochem. Biophys. Res. Commun. 304, 551–559.
Blomgren K., Zhu C., Wang X., et al. (2001) Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia: a mechanism of “pathological apoptosis”? J. Biol. Chem. 276, 10,191–10,198.
Chang Y. S., Mu D., Wendland M., et al. (2005) Erythropoietin improves functional and histological outcome in neonatal stroke. Pediatr. Res. 58, 106–111.
Comi A. M., Johnston M. V., and Wilson M. A. (2005) Strain variability, injury distribution, and seizure onset in a mouse model of stroke in the immature brain. Dev. Neurosci. 27, 127–133.
Comi A. M., Weisz C. J., Highet B. H., Johnston M. V., and Wilson M. A. (2004) A new model of stroke and ischemic seizures in the immature brain. Pediatr. Neurol. 31, 254–257.
Costeff H. (2004) Estimated frequency of genetic and nongenetic causes of congenital idiopathic cerebral palsy in west Sweden. Ann. Hum. Genet. 68, 515–520.
Crair M. C. and Malenka R. C. (1995) A critical period for long-term potentiation at thalamocortical synapses. Nature 375, 325–328.
Crothers B. and Paine R. S. (1988) The natural history of cerebral palsy. Mac Keith Press.
Culmsee C., Zhu C., Landshamer S., et al. (2005) Apoptosis-inducing factor triggered by poly (ADP-Ribose) polymerase and bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. J. Neurosci. 25, 10,262–10,272.
Dammann O. and Leviton A. (2004a) Biomarker epidemiology of cerebral palsy. Ann. Neurol. 55, 158–161.
Dammann O. and Leviton A. (2004b) Inflammatory brain damage in preterm newborns—dry numbers, wet lab, and causal inferences. Early Hum. Dev. 79, 1–15.
Dammann O., Drescher J., and Veelken N. (2003) Maternal fever at birth and non-verbal intelligence at age 9 years in preterm infants. Dev. Med. Child. Neurol. 45, 148–151.
Dawson V. L. and Dawson T. M. (2004) Deadly conversations: nuclear-mitochondrial cross-talk. J. Bioenerg. Biomembr. 36, 287–294.
De Vries L. S., VnHaastert I. L., Rademaker K. J., Koopman C., and Groenedaal F. (2004) Ultrasound abnormalities preceding cerebral palsy in highrisk preterm infants. J. Pediatr. 144, 815–820.
Derugin N., Wendland M., Muramatsu K., et al. (2000) Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats. Stroke 31, 1752–1761.
Du L., Zhang X., Han Y. Y., et al. (2003) Intra-mitochondrial poly(ADP-ribosylation) contributes to NAD+depletion and cell death induced by oxidative stress. J. Biol. Chem. 278, 18,426–18,433.
Elimian A., Figueroa R., Spitzer A. R., Ogburn P. L., Wiencek V., and Quirk J. G. (2003) Antenatal corticosteroids: are incomplete courses beneficial? Obstet. Gynecol. 102, 352–355.
Ellis M., Manandhar D. S., Manandhar N., Wyatt J., Bolam A. J., and Costello A. M. (2000) Stillbirths and neonatal encephalopathy in Kathmandu, Nepal: an estimate of the contribution of birth asphyxia to perinatal mortality in a low-income urban population. Paediatr. Perinat. Epidemiol. 14, 39–52.
Folkerth R. D. (2005) Neuropathologic substrate of cerebral palsy. J. Child. Neurol. 20, 940–949.
Folkerth R. D., Keefe R. J., Haynes R. L., Trachtenberg F. L., Volpe J. J., and Kinney H. C. (2004a) Interferon-gamma expression in periventricular leukomalacia in the human brain. Brain Pathol. 14, 265–274.
Folkerth R. D., Haynes R. L., Borenstein N. S., et al. (2004b) Developmental lag in superoxide dismutases relative to other antioxidant enzymes in premyelinated human telencephalic white matter. J. Neuropathol. Exp. Neurol. 63, 990–999.
Follett P. L., Rosenberg P. A., Volpe J. J., and Jensen F. E. (2000) NBQX attenuates excitotoxic injury in developing white matter. J. Neurosci. 20, 9235–9241.
Follett P. L., Deng W., Dai W., et al. (2004) Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J. Neurosci. 24, 4412–4420.
Gilland E., Puka-Sundvall M., Hillered L., and Hagberg H. (1998) Mitochondrial function and energy metabolism after hypoxia-ischemia in the immature rat brain: involvement of NMDA-receptors. J. Cereb. Blood Flow Metab. 18, 297–304.
Gluckman P. D., Wyatt J. S., Azzopardi D., et al. (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365, 663–670.
Golomb M. R. (2003) The contribution of prothrombotic disorders to peri- and neonatal ischemic stroke. Semin. Thromb. Hemost. 29, 415–424.
Golomb M. R., Dick P. T., MacGregor D. L., Curtis R., Sofronas M., and deVeber G. A. (2004) Neonatal arterial ischemic stroke and cerebral sinovenous thrombosis are more commonly diagnosed in boys. J. Child. Neurol. 19, 493–497.
Guan J., Bennet T. L., George S., et al. (2000) Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep. Neuroscience 95, 831–839.
Hagberg H. (2004) Mitochondrial impairment in the developing brain after hypoxia-ischemia. J. Bioenerg. Biomembr. 36, 369–373.
Hagberg H., Peebles D. and Mallard C. (2002) Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults. Ment. Retard. Dev. Disabil. Res. Rev. 8, 30–38.
Hagberg H., Lehmann A., Sandberg M., Nystrom B., Jacobson I., and Hamberger A. (1985) Ischemia-induced shift of inhibitory and excitatory amino acids from intra- to extracellular compartments. J. Cereb. Blood Flow Metab. 5, 413–419.
Hagberg H., Thornberg E., Blennow M., et al. (1993) Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy. Acta Paediatr. 82, 925–929.
Hagberg H., Wilson M. A., Matsushita H., et al. (2004) PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury. J. Neurochem. 90, 1068–1075.
Hamrick S. E., Miller S. P., Leonard C., et al. (2002) Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: the role of cystic periventricular leukomalacia. J. Pediatr. 145, 593–599.
Han B. H. and Holtzman D. M. (2000) BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway. J. Neurosci. 20, 5775–5781.
Han B. H., D'Costa A., Back S. A., et al. (2000) BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia. Neurobiol. Dis. 7, 38–53.
Hansen H. H., Briem T., Dzietko M., et al. (2004) Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain. Neurobiol. Dis. 16, 440–453.
Harum K. H., Hoon A. H. Jr., Kato G. J., Casella J. F., Breiter S. N., and Johnston M. V. (1999) Homozygous factor-V mutation as a genetic cause of perinatal thrombosis and cerebral palsy. Dev. Med. Child. Neurol. 41, 777–780.
Haynes R. L., Baud O., Li J., Kinney H. C., Volpe J. J., and Folkerth D. R. (2005) Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol. 15, 225–233.
Haynes R. L., Folkerth R. D., Keefe R. J., et al. (2003) Nitrosative and oxidative injury to premyelinating oligodendrocytes in periventricular leukomalacia. J. Neuropathol. Exp. Neurol. 62, 441–450.
Hoon A. H. Jr. (1995) Neuroimaging in the high-risk infant: relationship to outcome. J. Perinatol. 15, 389–394.
Hoon A. H. Jr. (2005) Neuroimaging in cerebral palsy: patterns of brain dysgenesis and injury. J. Child. Neurol. 20, 936–939.
Hoon A. H. Jr., Belsito K. M., and Nagae-Poetscher L. M. (2003) Neuroimaging in spasticity and movement disorders. J. Child. Neurol. 18(Suppl.), S25-S39.
Hoon A. H. Jr., Lawrie W. T. Jr., Melhem E. R., et al. (2002) Diffusion tensor imaging of periventricular leukomalacia shows affected sensory cortex white matter pathways. Neurology 59, 752–756.
Hoon A. H. Jr., Reinhardt E. M., Kelley R. I., et al. (1997) Brain magnetic resonance imaging in suspected extrapyramidal cerebral palsy: observations in distinguishing genetic-metabolic from acquired causes. J. Pediatr. 131, 240–245.
Hu B. R., Liu C. L., Ouvang Y., Blomgren A. M., and Siesjo B. K. (2000) Involvement of caspase 3 in cell death after hypoxia-ischemia declines during brain maturation. J. Cereb. Blood Flow Metab. 20, 1294–1300.
Husson I., Rangon C. M., Lelievre V., et al. (2005) BDNF-induced white matter neuroprotection and stage-dependent neuronal survival following a neonatal excitotoxic challenge. Cereb. Cortex 15, 250–261.
Inder T. E., Anderson N. J., Spencer C., Wells S., and Volpe J. J. (2003) White matter injury in the premature infant: comparison between serial cranial ultrasonographic and MR findings at term. Am. J. Neuroradiol. 24, 805–809.
Inder T. E., Warfield S. K., Wang H., Huppi P. S., and Volpe J. J. (2005) Abnormal cerebral structure is present at term in premature infants. Pediatrics, 115, 286–294.
Ishida A., Trescher W. H., Lange M. S., and Johnston M. V. (2001a) Prolonged suppression of brain nitric oxide synthase activity by 7-nitroindazole protects against cerebral hypoxic-ischemic injury in neonatal rat. Brain Dev. 23, 349–354.
Ishida A., Ishiwa S., Trescher W. H., et al. (2001b) Delayed increase in neuronal nitric oxide synthase immunoreactivity in thalamus and other brain regions after hypoxic-ischemic injury in neonatal rats. Exp. Neurol. 168, 323–333.
Jarvis S., Glinianaia S. V., Arnaud C., et al. (2005) Case gender and severity in cerebral palsy varies with intrauterine growth. Arch. Dis. Child. 90, 474–479.
Jensen F. E. (2002) The role of glutamate receptor maturation in perinatal seizures and brain injury. Int. J. Dev. Neurosci. 20, 339–347.
Jensen F. E. (2005) Role of glutamate receptors in periventricular leukomalacia. J. Child. Neurol. 20, 950–959.
Johnston B. M., Mallard E. C., Williams C. E., and Gluckman P. D. (1996) Insulin-like growth factor-1 is a potent neuronal rescue agent after hypoxicischemic injury in fetal lambs. J. Clin. Invest. 97, 300–308.
Johnston M. V. (2005) Excitotoxicity in perinatal brain injury. Brain Pathol. 15, 234–240.
Johnston M. V. and Hoon A. H. Jr. (2000) Possible mechanisms in infants for selective basal ganglia damage from asphyxia kernicterus, or mitochondrial encephalopathies. J. Child. Neurol. 15, 588–591.
Johnston M. V., Nakajima W., and Hagberg H. (2002) Mechanisms of hypoxic neurodegeneration in the developing brain. Neuroscientist. 8, 212–220.
Johnston M. V., Ferriero D. M., Vannucci S. J., and Hagberg H. (2005) Models of cerebral palsy: which ones are best? J. Child. Neurol. 20, 984–987.
Johnston M. V., Trescher W. H., Ishida A., and Nakajima W. (2000) Novel treatments after experimental brain injury. Semin. Neonatol. 5 75–86.
Johnston M. V., Trescher W. H., Ishida A., and Nakajima W. (2001) Neurobiology of hypoxic-ischemic injury in the developing brain. Pediatr. Res. 49, 735–741.
Karadottir R., Cavelier P., Bergersen L. H., and Attwell D. (2005) NMDA receptors are expressed in oligo-dendrocytes and activated in ischaemia. Nature 438, 1162–1166.
Kent A., Lomas F., Hurrion E., and Dahlstrom J. E. (2005) Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: neurodevelopmental outcome and chorioamnionitis in premature infants. J. Paediatr. Child. Health 41, 186–190.
Kuban K. C. K. and Leviton A. (1996) Cerebral palsy. N. Engl. J. Med. 330, 188–195.
LaFranchi S. H., Haddow J. E., and Hollowell J. G. (2005) Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes? Thyroid. 15, 60–71.
Lee H. T., Chang Y. C., Wang L. Y., Wang S. T., Huang C. C., and Ho C. J. (2004) cAMP response element-binding protein activation in ligation preconditioning in neonatal brain. Ann. Neurol. 56, 611–623.
Li H., Pin S., Zeng Z., Wang M. M., Andreasson K. A., and McCullough L. D. (2005) Sex differences in cell death. Ann. Neurol. 58, 317–321.
Li J. H. and Zhang J. (2001) PARP inhibitors. I Drugs 4, 804–812.
Liu Y., Barks J. D., Xu G., and Silverstein F. S. (2004) Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats. Stroke 35, 1460–1465.
Ma D., Hossain M., Chow A., et al. (2005) Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. Ann. Neurol. 58, 182–193.
Magistretti P. J., Pellerin L., Rothman D. L., and Shulman R. G. (1999) Energy on demand. Science 283, 496–497.
Mallard C., Welin A. K., Peebles D., Hagberg H., and Kjellmer I. (2003) White matter injury following systemic endotoxemia or asphyxia in the fetal sheep. Neurochem. Res. 28, 215–223.
Marlow N. (2004) Neurocognitive outcome after very preterm birth. Arch. Dis. Child. Fetal Neonatal Ed. 89, F224-F228.
Martin L. J., Al-Abdulla N. A., Brambrink A. M., et al. (1998) Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: a perspective on the contributions of a poptosis and necrosis. Brain Res. Bull. 46, 281–309.
Matsushita H., Johnston M. V., Lange M. S. and Wilson M. A. (2003) Protective effect of erythropoietin in neonatal hypoxic ischemia in mice. Neuroreport. 14, 1757–1761.
McCullough L. D., Zeng Z., Blizzard K. K., Debchoudhury I., and Hurn P. D. (2005) Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection. J. Cereb. Blood Flow Metab. 25, 502–512.
McDonald J. W. and Johnston M. V. (1990) Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res. Brain Res. Rev. 15, 41–70.
McDonald J. W., Silverstein F. S., and Johnston M. V. (1987) MK-801 protects the neonatal brain from hypoxic-ischemic damage. Eur. J. Pharmacol. 140, 359–361.
McDonald J. W., Silverstein F. S., and Johnston, M. V. (1988) Neurotoxicity of N-methyl-d-aspartate is markedly enhanced in developing rat central nervous system. Brain Res. 459, 200–203.
McQuillen P. S., Sheldon R. A., Shatz C. J., and Ferriero D. M. (2003) Selective vulnerability of subplate neurons after early neonatal hypoxia-ischemia. J. Neurosci. 23, 3308–3315.
Melhem E. R., Hoon A. H. Jr., Ferrucci J. T. Jr., et al. (2000) Periventricular leukomalacia: relationship between lateral ventricular volume on brain MR images and severity of cognitive and motor impairment. Radiology 214 199–204.
Ment L. R., Oh W., Ehrenkranz R. A., Philip A. G., Duncan C. C., and Makuch R. W. (1995) Antenatal steroids, delivery mode, and intraventricular hemorrhage in preterm infants. Am. J. Obstet. Gynecol. 172, 795–800.
Ment L. R., Vohr B. R., Makuch R. W., et al. (2004) Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J. Pediatr. 145, 832–834.
Micu I., Jiang Q., Coderre E., et al. (2006) NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature 439, 988–992.
Mikkola K., Ritari N., Tommiska V., et al. (2006) Neuro-developmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996–1997. Pediatrics. 116, 1391–1400.
Mishra O. P. and Delivoria-Papadopoulos M. (2002) Nitric oxide-mediated Ca2+-influx in neuronal nuclei and cortical synaptosomes of normoxic and hypoxic newborn piglets. Neurosci. Lett. 318, 93–97.
Monyer H., Brunashev N., and Laurie D. J. (1993) Development and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 12, 529–540.
Nakajima W., Ishida A., Lange M.S., et al. (2000) A poptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat. J. Neurosci. 20, 7994–8004.
Nelson K. B. and Ellenberg J. H. (1986) Antecedents of cerebral palsy. Multivariate analysis of risk. N. Engl. J. Med. 315, 81–86.
Nelson K. B. and Lynch J. K. (2006) Stroke in newborn infants. Lancet Neurol. 3, 150–158.
Nelson K. B., Grether J. K., Dambrosia J. M., et al. (2003) Neontal cytokines and cerebral palsy in very preterm infants. Pediatr. Res. 53, 600–607.
Northington F. J., Ferriero D. M., Flock D. L., and Martin L. J. (2001) Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is a poptosis. J. Neurosci. 21, 1931–1938.
Oka A., Belliveau M. J., Rosenberg P. A., and Volpe J. J. (1993) Vulnerability of oligodendroglial to glutamate: pharmacology, mechanisms, and prevention. J. Neurosci. 13, 1441–1453.
Osler W. (1987) The cerebral palsies of children. Mac Keith Press. London.
Papile L. A., Munsick-Bruno G., and Schaefer A. (1983) Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J. Pediatr. 103, 273–277.
Pasternak J. F. and Gorey M. T. (1998) The syndrome of acute near-total intrauterine asphyxia in the term infant. Pediatr. Neurol. 18, 391–398.
Perlman J. M. (1998) White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome. Early Hum. Dev. 53, 99–120.
Plesnila N. (2004) Role of mitochondrial proteins for neuronal cell death after focal cerebral ischemia. Acta Neurochir. (Suppl. 89), 15–19.
Plesnila N., Zhu C., Culmsee C., Groger M., Moskowitz M. A., and Blomgren K. (2004) Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia. J. Cereb. Blood Flow Metab. 24, 458–466.
Pu Y., Li Q. F., Zeng C. M., et al. (2000) Increased detectability of alpha brain glutamate/glutamine in neonatal hypoxic-ischemic encephalopathy. AJNR Am. J. Neuroradiol. 21, 203–212.
Puka-Sundvall M., Gajkowska B., Cholewinski M., Blomgren K., Lazarewicz J. W., and Hagberg H. (2000) Subcellular distribution of calcium and ultrastructural changes after cerebral hypoxia-ischemia in immature rats. Brain Res. Dev. Brain Res. 125, 31–41.
Reiss A. L., Kesler S. R., Vohr B., et al. (2004) Sex differences in cerebral volumes of 8-year-olds born preterm. J. Pediatr. 145, 242–249.
Riikonen R. S., Kero P. O., and Simell O. G. (1992) Excitatory amino acids in cerebrospinal fluid in neonatal asphyxia. Pediatr. Neurol. 8, 37–40.
Roland E. H. and Hill A. (2003) Germinal matrix-intraventricular hemorrhage in the premature newborn: management and outcome. Neurol. Clin. 21, 833–851.
Rosenberg P. A., Dai W., Gan X. D. et al. (2003) Mature myelin basic protein-expressing oligodendrocytes are insensitive to kainate toxicity. J. Neurosci. Res. 71, 237–245.
Salter M. G. and Fern R. (2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438, 1167–1171.
Shankaran S., Laptook A. R., Ehrenkranz R. A., et al. (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N. Engl. J. Med. 353, 1574–1584.
Silverstein F. S., Buchanan K., and Johnston M. V. (1986) Perinatal hypoxia-ischemia disrupts striatal high-affinity [3H]glutamate uptake into synaptosomes. J. Neurochem. 47, 1614–1619.
Tahraoui S. L., Marret S., Bodenant C., et al. (2001) Central role of microglia in neonatal excitotoxic lesions of the murine periventricular white matter. Brain Pathol. 11, 56–71.
Tanaka S., Takehashi M., Iida S., et al. (2005) Mitochondrial impairment induced by poly (ADP-ribose) polymerase-1 activation in cortical neurons after oxygen and glucose deprivation. J. Neurochem. 95, 179–190.
Thomas B., Eyssen M., Peeters R., et al. (2005) Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury. Brain 128, 2562–2577.
Thoresen M., Satas S., Puka-Sundvall M., et al. (1997) Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins. Neuroreport 8, 3359–3362.
Utiger R. D. (1999) Maternal hypothyroidism and fetal development (Editorial). N. Engl. J. Med. 341, 601–602.
Volpe J. (2003) Cerebral white matter injury of the premature infant—more common than you think. Pediatrics 112, 176–180.
Volpe J. J. (2001) Neurobiology of periventricular leukomalacia in the premature infant. Pediatr. Res. 50, 553–562.
Willoughby R. E. and Nelson K. B. (2002) Chorioamnionitis and brain injury. Clin. Perinatol. 29, 603–621.
Woodward L. J., Edgin J. O., Thompson D., and Inder T. E. (2005) Object working memory deficits predicted by early brain injury and development of the preterm infant. Brain. 128, 2578–2587.
Xu Y., Huang S., Liu Z. G., and Han J. (2006) Poly (ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation. J. Biol. Chem. 281, 8788–8795.
Yamaguchi S., Endo K., Kitajima T., Ogata H., and Hori Y. (1998) Involvement of the glutamate transporter and the sodium-calcium exchanger in the hypoxia-induced increase in intracellular Ca2+ in rat hippocampal slices. Brain Res. 813, 351–358.
Zhu C., Qiu L., Wang X., et al. (2003) Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain. J. Neurochem. 86, 306–317.
Zhu C., Xu F., Wang X., et al. (2006) Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia. J. Neurochem. 96, 1016–1027.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Johnston, M.V., Hoon, A.H. Cerebral palsy. Neuromol Med 8, 435–450 (2006). https://doi.org/10.1385/NMM:8:4:435
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/NMM:8:4:435