{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:05:29Z","timestamp":1793318729737,"version":"4.5.0"},"reference-count":62,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,7,1]]},"DOI":"10.1542\/peds.112.1.176","type":"journal-article","created":{"date-parts":[[2004,8,14]],"date-time":"2004-08-14T00:43:47Z","timestamp":1092444227000},"page":"176-180","source":"Crossref","is-referenced-by-count":429,"title":["Cerebral White Matter Injury of the Premature Infant\u2014More Common Than You Think"],"prefix":"10.1542","volume":"112","author":[{"given":"Joseph J.","family":"Volpe","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital&#x2028; Harvard Medical School&#x2028; Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2003,7,1]]},"reference":[{"key":"2021121003400477700_R1","unstructured":"Volpe JJ. Neurology of the Newborn, 4th ed. Philadelphia, PA: WB Saunders; 2001"},{"key":"2021121003400477700_R2","doi-asserted-by":"crossref","unstructured":"Bracewell M, Marlow N. Patterns of motor disability in very preterm children. MRRD Res Rev.2002;8:241\u2013248","DOI":"10.1002\/mrdd.10049"},{"key":"2021121003400477700_R3","doi-asserted-by":"crossref","unstructured":"Aylward GP. Cognitive and neuropsychological outcomes: more than IQ scores. MRDD Res Rev.2002;8:234\u2013240","DOI":"10.1002\/mrdd.10043"},{"key":"2021121003400477700_R4","doi-asserted-by":"crossref","unstructured":"Wood NS, Markow N, Costeloe K, Gibson AT, Wilkinson AR. Neurologic and developmental disability after extremely preterm birth. N Engl J Med.2000;343:378\u2013384","DOI":"10.1056\/NEJM200008103430601"},{"key":"2021121003400477700_R5","doi-asserted-by":"crossref","unstructured":"Hack M, Wilson-Costello D, Friedman H, Taylor GH, Schluchter M, Fanaroff AA. Neurodevelopment and predictors of outcomes of children with birth weights of less than 1000 g. Arch Pediatr Adolesc Med.2000;154:725\u2013731","DOI":"10.1001\/archpedi.154.7.725"},{"key":"2021121003400477700_R6","doi-asserted-by":"crossref","unstructured":"Counsell SJ, Allsop JM, Harrison MC, et al. Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality. Pediatrics.2003;112:1\u20137","DOI":"10.1542\/peds.112.1.1"},{"key":"2021121003400477700_R7","doi-asserted-by":"crossref","unstructured":"Banker BQ, Larroche JC. Periventricular leukomalacia of infancy. Arch Neurol.1962;7:386\u2013410","DOI":"10.1001\/archneur.1962.04210050022004"},{"key":"2021121003400477700_R8","unstructured":"Inder TE, Anderson NJ, Spencer C, Wells SJ, Volpe J White matter injury in the premature infant: a comparison between serial cranial ultrasound and MRI at term. AJNR.2003. In press"},{"key":"2021121003400477700_R9","doi-asserted-by":"crossref","unstructured":"Maalouf EF, Duggan PJ, Counsell S, et al. Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants. Pediatrics.2001;107:719\u2013727","DOI":"10.1542\/peds.107.4.719"},{"key":"2021121003400477700_R10","doi-asserted-by":"crossref","unstructured":"Gilles FH, Leviton A, Dooling EC. The Developing Human Brain: Growth and Epidemiologic Neuropathology. Boston, MA: John Wright, Inc; 1983","DOI":"10.1016\/B978-0-7236-7017-9.50007-7"},{"key":"2021121003400477700_R11","doi-asserted-by":"crossref","unstructured":"Gilles FH, Murphy SF. Perinatal telencephalic leucoencephalopathy. J Neurol Neurosurg Psychiatry.1969;32:404\u2013413","DOI":"10.1136\/jnnp.32.5.404"},{"key":"2021121003400477700_R12","doi-asserted-by":"crossref","unstructured":"Maalouf EF, Duggan PJ, Rutherford MA, et al. Magnetic resonance imaging of the brain in a cohort of extremely preterm infants. J Pediatr.1999;135:351\u2013357","DOI":"10.1016\/S0022-3476(99)70133-2"},{"key":"2021121003400477700_R13","doi-asserted-by":"crossref","unstructured":"Neil JJ, Shiran SI, McKinstry RC, et al. Normal brain in human newborns: apparent diffusion coefficient and diffusion anisotropy measured by using diffusion tensor MR imaging. Radiology.1998;209:57\u201366","DOI":"10.1148\/radiology.209.1.9769812"},{"key":"2021121003400477700_R14","doi-asserted-by":"crossref","unstructured":"Huppi PS, Maier SE, Peled S, et al. Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Pediatr Res.1998;44:584\u2013590","DOI":"10.1203\/00006450-199810000-00019"},{"key":"2021121003400477700_R15","doi-asserted-by":"crossref","unstructured":"Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci.2001;21:1302\u20131312","DOI":"10.1523\/JNEUROSCI.21-04-01302.2001"},{"key":"2021121003400477700_R16","doi-asserted-by":"crossref","unstructured":"Back SA, Luo NL, Borenstein NS, Volpe JJ, Kinney HC. Arrested oligodendrocyte lineage progression during human cerebral white matter development: dissociation between the timing of progenitor differentiation and myelinogenesis. J Neuropathol Exper Neurol.2002;61:197\u2013211","DOI":"10.1093\/jnen\/61.2.197"},{"key":"2021121003400477700_R17","doi-asserted-by":"crossref","unstructured":"Kinney HC, Brody BA, Kloman AS, Gilles FH. Sequence of central nervous system myelination in human infancy. II. Patterns of myelination in autopsied infants. J Neuropathol Exp Neurol.1988;47:217\u2013234","DOI":"10.1097\/00005072-198805000-00003"},{"key":"2021121003400477700_R18","doi-asserted-by":"crossref","unstructured":"Wimberger DM, Roberts TP, Barkovich AJ, Prayer LM, Moseley ME, Kucharczyk J. Identification of \u201cpremyelination\u201d by diffusion-weighted MRI. J Comput Assist Tomogr.1995;19:28\u201333","DOI":"10.1097\/00004728-199501000-00005"},{"key":"2021121003400477700_R19","doi-asserted-by":"crossref","unstructured":"Hildebrand C, Waxman SG. Postnatal differentiation of rat optic nerve fibers: electron microscopic observations on the development of nodes of Ranvier and axoglial relations. J Comp Neurol.1984;224:25\u201337","DOI":"10.1002\/cne.902240103"},{"key":"2021121003400477700_R20","doi-asserted-by":"crossref","unstructured":"Fields RD, Waxman SG. Regional membrane heterogeneity in premyelinated CNS axons: factors influencing the binding of sterol-specific probes. Brain Res.1988;443:231\u2013242","DOI":"10.1016\/0006-8993(88)91617-4"},{"key":"2021121003400477700_R21","doi-asserted-by":"crossref","unstructured":"Black JA, Waxman SG, Ransom BR, Feliciano MD. A quantitative study of developing axons and glia following altered gliogenesis in rat optic nerve. Brain Res.1986;380:122\u2013135","DOI":"10.1016\/0006-8993(86)91436-8"},{"key":"2021121003400477700_R22","doi-asserted-by":"crossref","unstructured":"Waxman SG, Black JA, Kocsis JD, Ritchie JM. Low density of sodium channels supports action potential conduction in axons of neonatal rat optic nerve. Proc Natl Acad Sci USA.1989;86:1406\u20131410","DOI":"10.1073\/pnas.86.4.1406"},{"key":"2021121003400477700_R23","doi-asserted-by":"crossref","unstructured":"Haynes RL, Folkerth RD, Keefe R, et al. Nitrosative and oxidative injury to premyelinating oligodendrocytes is accompanied by microglial activation in periventricular leukomalacia in the human premature infant. J Neuropath Exp Neurol.2003. In press","DOI":"10.1093\/jnen\/62.5.441"},{"key":"2021121003400477700_R24","doi-asserted-by":"crossref","unstructured":"Inder TE, Huppi PS, Warfield S, et al. Periventricular white matter injury in the premature infant is associated with a reduction in cerebral cortical gray matter volume at term. Ann Neurol.1999;46:755\u2013760","DOI":"10.1002\/1531-8249(199911)46:5<755::AID-ANA11>3.0.CO;2-0"},{"key":"2021121003400477700_R25","doi-asserted-by":"crossref","unstructured":"Inder TE, Mocatta T, Darlow B, Spencer C, Volpe JJ. Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury. Pediatr Res.2002;52:213\u2013218","DOI":"10.1203\/00006450-200208000-00013"},{"key":"2021121003400477700_R26","doi-asserted-by":"crossref","unstructured":"Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res.2001;50:553\u2013562","DOI":"10.1203\/00006450-200111000-00003"},{"key":"2021121003400477700_R27","doi-asserted-by":"crossref","unstructured":"Hagberg H, Peebles D, Mallard C. Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults. MRDD Res Rev.2002;8:30\u201338","DOI":"10.1002\/mrdd.10007"},{"key":"2021121003400477700_R28","doi-asserted-by":"crossref","unstructured":"Skoff RP, Bessert DA, Barks JDE, Song DK, Cerghet M, Silverstein FS. Hypoxic-ischemic injury results in acute disruption of myelin gene expression and death of oligodendroglial precursors in neonatal mice. Int J Devl Neurosci.2001;19:197\u2013208","DOI":"10.1016\/S0736-5748(00)00075-7"},{"key":"2021121003400477700_R29","doi-asserted-by":"crossref","unstructured":"Cai ZW, Pang Y, Xiao F, Rhodes PG. Chronic ischemia preferentially causes white matter injury in the neonatal rat brain. Brain Res.2001;898:126\u2013135","DOI":"10.1016\/S0006-8993(01)02180-1"},{"key":"2021121003400477700_R30","doi-asserted-by":"crossref","unstructured":"Levison SW, Rothstein RP, Romanko MJ, Snyder MJ, Meyers RL, Vannucci SJ. Hypoxia-ischemia depletes the rat perinatal subventricular zone of oligodendrocyte progenitors and neural stem cells. Dev Neurosci.2001;23:234\u2013247","DOI":"10.1159\/000046149"},{"key":"2021121003400477700_R31","doi-asserted-by":"crossref","unstructured":"Liu Y, Silverstein FS, Skoff R, Barks JDE. Hypoxic-ischemic oligodendroglial injury in neontal rat brain. Pediatr Res.2002;51:25\u201333","DOI":"10.1203\/00006450-200201000-00007"},{"key":"2021121003400477700_R32","doi-asserted-by":"crossref","unstructured":"Petersson KH, Pinar H, Stopa EG, et al. White matter injury after cerebral ischemia in ovine fetuses. Pediatr Res.2002;51:768\u2013776","DOI":"10.1203\/00006450-200206000-00019"},{"key":"2021121003400477700_R33","doi-asserted-by":"crossref","unstructured":"Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci.2002;22:455\u2013463","DOI":"10.1523\/JNEUROSCI.22-02-00455.2002"},{"key":"2021121003400477700_R34","doi-asserted-by":"crossref","unstructured":"Ivacko JA, Sun R, Silverstein FS. Hypoxic-ischemic brain injury induces an acute microglial reaction in perinatal rats. Pediatr Res.1995;39:39\u201347","DOI":"10.1203\/00006450-199601000-00006"},{"key":"2021121003400477700_R35","doi-asserted-by":"crossref","unstructured":"Bona E, Andersson A-L, Blomgren K, et al. Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. Pediatr Res.1999;45:500\u2013509","DOI":"10.1203\/00006450-199904010-00008"},{"key":"2021121003400477700_R36","doi-asserted-by":"crossref","unstructured":"Possel H, Noack H, Putzke J, Wolf G, Sies H. Selective upregulation of inducible nitric oxide synthase (INOS) by lipopolysaccharide (LPS) and cytokines in microglia: in vitro and in vivo studies. Glia.2000;32:51\u201359","DOI":"10.1002\/1098-1136(200010)32:1<51::AID-GLIA50>3.0.CO;2-4"},{"key":"2021121003400477700_R37","doi-asserted-by":"crossref","unstructured":"Chao CC, Hu S, Molitor TW, Shaskan EG, Peterson PK. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol.1992;149:2736\u20132741","DOI":"10.4049\/jimmunol.149.8.2736"},{"key":"2021121003400477700_R38","unstructured":"Colton CA, Gilbert DL. Microglia, an in vivo source of reactive oxygen species in the brain. Adv Neurol.1993;59:321\u2013326"},{"key":"2021121003400477700_R39","doi-asserted-by":"crossref","unstructured":"Back SA, Gan X, Li Y, Rosenberg PR, Volpe JJ. Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci.1998;18:6241\u20136253","DOI":"10.1523\/JNEUROSCI.18-16-06241.1998"},{"key":"2021121003400477700_R40","unstructured":"Baud O, Haynes RL, Volpe JJ, Rosenberg PA. Developmental upregulation of manganese superoxide dismutase (MnSOD) expression in oligodendrocytes (OLs) confers resistance to nitric oxide toxicity. Abstr Soc Neurosci.2003. In press"},{"key":"2021121003400477700_R41","doi-asserted-by":"crossref","unstructured":"Mackenzie-Graham AJ, Mitrovic B, Smoll A, Merrill JE. Differential sensitivity to nitric oxide in immortalized, cloned murine oligodendrocyte cell lines. Dev Neurosci.1994;16:162\u2013171","DOI":"10.1159\/000112103"},{"key":"2021121003400477700_R42","doi-asserted-by":"crossref","unstructured":"Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol.1993;151:2132\u20132141","DOI":"10.4049\/jimmunol.151.4.2132"},{"key":"2021121003400477700_R43","doi-asserted-by":"crossref","unstructured":"Yoshioka A, Bacskai B, Pleasure D. Pathophysiology of oligodendroglial excitotoxicity. J Neurosci Res.1996;46:427\u2013438","DOI":"10.1002\/(SICI)1097-4547(19961115)46:4<427::AID-JNR4>3.0.CO;2-I"},{"key":"2021121003400477700_R44","doi-asserted-by":"crossref","unstructured":"Sanchez-Gomez MV, Matute C. AMPA and kainate receptors each mediate excitotoxicity in oligodendroglial cultures. Neurobiol Dis.1999;6:475\u2013485","DOI":"10.1006\/nbdi.1999.0264"},{"key":"2021121003400477700_R45","doi-asserted-by":"crossref","unstructured":"Follett PL, Rosenberg PA, Volpe JJ, Jensen FE. NBQX attenuates excitotoxic injury in developing white matter. J Neurosci.2000;20:9235\u20139241","DOI":"10.1523\/JNEUROSCI.20-24-09235.2000"},{"key":"2021121003400477700_R46","doi-asserted-by":"crossref","unstructured":"Yoshioka A, Yamaya Y, Saiki S, et al. Non-N-methyl-D-aspartate glutamate receptors mediate oxygen-glucose deprivation-induced oligodendroglial injury. Brain Res.2000;854:207\u2013215","DOI":"10.1016\/S0006-8993(99)02359-8"},{"key":"2021121003400477700_R47","doi-asserted-by":"crossref","unstructured":"Fern R, Moller T. Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci.2000;20:34\u201342","DOI":"10.1523\/JNEUROSCI.20-01-00034.2000"},{"key":"2021121003400477700_R48","doi-asserted-by":"crossref","unstructured":"Matute C, Alberdi E, Domercq M, Perez-Cerda F, Perez-Samartin A, Sanchez-Gomez MV. The link between excitotoxic oligodendroglial death and demyelinating diseases. Trends Neurosci.2001;24:224\u2013230","DOI":"10.1016\/S0166-2236(00)01746-X"},{"key":"2021121003400477700_R49","doi-asserted-by":"crossref","unstructured":"Xu HY, Barks JDE, Liu YQ, Silverstein FS. AMPA-Induced suppression of oligodendroglial gene expression in neonatal rat brain. Brain Res Dev Brain Res.2001;132:175\u2013178","DOI":"10.1016\/S0165-3806(01)00306-6"},{"key":"2021121003400477700_R50","doi-asserted-by":"crossref","unstructured":"Liu H-N, Giasson BI, Mushynski WE, Almazan G. AMPA receptor-mediated toxicity in oligodendrocyte progenitors involves free radical generation and activation of JNK, calpain and caspase 3. J Neurochem.2002;82:398\u2013409","DOI":"10.1046\/j.1471-4159.2002.00981.x"},{"key":"2021121003400477700_R51","doi-asserted-by":"crossref","unstructured":"Rosenberg PA, Dai W, Gan XD, et al. Mature myelin basic protein expressing oligodendrocytes are insensitive to kainate toxicity. J Neurosci Res.2003;71:237\u2013245","DOI":"10.1002\/jnr.10472"},{"key":"2021121003400477700_R52","doi-asserted-by":"crossref","unstructured":"Pang Y, Cai ZW, Rhodes PG. Effects of lipopolysaccharide on oligodendrocyte progenitor cells are mediated by astrocytes and microglia. J Neurosci.2000;62:510\u2013520","DOI":"10.1002\/1097-4547(20001115)62:4<510::AID-JNR5>3.0.CO;2-F"},{"key":"2021121003400477700_R53","doi-asserted-by":"crossref","unstructured":"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\u201371","DOI":"10.1111\/j.1750-3639.2001.tb00381.x"},{"key":"2021121003400477700_R54","doi-asserted-by":"crossref","unstructured":"Colton CA, Gilbert DL. Production of superoxide anions by a CNS macrophage, the microglia. FEBS Lett.1987;223:284\u2013288","DOI":"10.1016\/0014-5793(87)80305-8"},{"key":"2021121003400477700_R55","doi-asserted-by":"crossref","unstructured":"Klegeris A, McGeer PL. Rat brain microglia and peritoneal macrophages show similar responses to respiratory burst stimulants. J Neuroimmunol.1994;53:83\u201390","DOI":"10.1016\/0165-5728(94)90067-1"},{"key":"2021121003400477700_R56","doi-asserted-by":"crossref","unstructured":"Tanaka M, Sotomatsu A, Yoshida T, Hirai S, Nishida A. Detection of superoxide production of activated microglia using a sensitive and specific chemiluminescence assay and microglia-mediated PC12h cell death. J Neurochem.1994;63:266\u2013270","DOI":"10.1046\/j.1471-4159.1994.63010266.x"},{"key":"2021121003400477700_R57","doi-asserted-by":"crossref","unstructured":"Xie Z, Wei M, Morgan TE, et al. Peroxynitrite mediates neurotoxicity of amyloid \u03b2-peptide 1\u201342- and lipopolysaccharide-activated microglia. J Neurosci.2002;22:3484\u20133492","DOI":"10.1523\/JNEUROSCI.22-09-03484.2002"},{"key":"2021121003400477700_R58","doi-asserted-by":"crossref","unstructured":"Zhang GL, Ghosh S. Toll-like receptor-mediated NF-\u03baB activation: a phylogenetically conserved paradigm in innate immunity. J Clin Invest.2001;107:13\u201319","DOI":"10.1172\/JCI11837"},{"key":"2021121003400477700_R59","doi-asserted-by":"crossref","unstructured":"Hallman M, Ramet M, Ezekowitz RA. Toll-like receptors as sensors of pathogens. Pediatr Res.2001;50:315\u2013321","DOI":"10.1203\/00006450-200109000-00004"},{"key":"2021121003400477700_R60","doi-asserted-by":"crossref","unstructured":"Lehnardt S, Lachance C, Patrizi S, et al. The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci.2002;22:2478\u20132486","DOI":"10.1523\/JNEUROSCI.22-07-02478.2002"},{"key":"2021121003400477700_R61","doi-asserted-by":"crossref","unstructured":"Eklind S, Mallard C, Leverin A-L, et al. Bacterial endotoxin sensitizes the immature brain to hypoxic-ischaemic injury. Eur J Neurosci.2001;13:1101\u20131106","DOI":"10.1046\/j.0953-816x.2001.01474.x"},{"key":"2021121003400477700_R62","doi-asserted-by":"crossref","unstructured":"Tsuji M, Saul JP, du Plessis A, et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics.2000;106:625\u2013632","DOI":"10.1542\/peds.106.4.625"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/112\/1\/176\/1002339\/pe0703000176.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/112\/1\/176\/1002339\/pe0703000176.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T05:39:35Z","timestamp":1682746775000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/112\/1\/176\/63400\/Cerebral-White-Matter-Injury-of-the-Premature"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,7,1]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2003,7,1]]},"published-print":{"date-parts":[[2003,7,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.112.1.176","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,7,1]]}}}