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The classic neuropathology of PVL has given rise to several hypotheses about the pathogenesis, largely relating to hypoxia-ischemia and reperfusion in the sick premature infant. These include free radical injury, cytokine toxicity (especially given the epidemiologic association of PVL with maternofetal infection), and excitotoxicity. Among the recent findings directly in human postmortem tissue is that immunocytochemical markers of lipid peroxidation (hydroxy-nonenal and malondialdehyde) and protein nitration (nitrotyrosine) are significantly increased in PVL. Premyelinating oligodendrocytes, which predominate in periventricular regions during the window of vulnerability to PVL (24 to 34 postconceptional weeks), are the targets of this free radical injury, and suffer cell death. Susceptibility can be attributed, at least in part, to a relative deficiency of superoxide dismutases in the preterm white matter, including premyelinating oligodendrocytes. Several cytokines, including interferon-\u03b3 (known to be directly toxic to immature oligodendroglia in vitro), as well as tumor necrosis factor-\u03b1 and interleukins 2 and 6, have been demonstrated in PVL. Microglia, which express toll-like receptors to bacterial products such as lipopolysaccharide, are increased in PVL white matter and may contribute to the injury. Preliminary work suggests a role for glutamate receptors and glutamate transporters in PVL, as has been seen in experimental animals. These findings pave the way for eventual therapeutic or preventive strategies for PVL.<\/jats:p>","DOI":"10.2350\/06-01-0024.1","type":"journal-article","created":{"date-parts":[[2006,7,12]],"date-time":"2006-07-12T17:06:23Z","timestamp":1152723983000},"page":"3-13","source":"Crossref","is-referenced-by-count":90,"title":["Periventricular Leukomalacia: Overview and Recent Findings"],"prefix":"10.1177","volume":"9","author":[{"given":"Rebecca D.","family":"Folkerth","sequence":"first","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Department of Neuropathology, Children's Hospital, and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2006,1,1]]},"reference":[{"key":"bibr1-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(95)00192-1"},{"key":"bibr2-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.5.441"},{"key":"bibr3-06-01-0024.1","first-page":"29","volume-title":"Pathology and Genetics: Acquired and Inherited Diseases of the Developing Nervous System","author":"Kinney HC","year":"2004"},{"key":"bibr4-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.1.176"},{"key":"bibr5-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00008403"},{"key":"bibr6-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1996.tb15068.x"},{"key":"bibr7-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1998.tb10231.x"},{"key":"bibr8-06-01-0024.1","first-page":"3","volume":"12","author":"Bejar RF","year":"1992","journal-title":"J Perinatol"},{"key":"bibr9-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.97.6.822"},{"key":"bibr10-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1962.04210050022004"},{"key":"bibr11-06-01-0024.1","volume-title":"Neurology of the Newborn","author":"Volpe JJ","year":"2001"},{"key":"bibr12-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.4.719"},{"key":"bibr13-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1136\/fn.88.4.F269"},{"key":"bibr14-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160102"},{"key":"bibr15-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1067\/S0022-3476(03)00357-3"},{"key":"bibr16-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(96)02780-4"},{"key":"bibr17-06-01-0024.1","first-page":"1243","volume":"47","author":"Ibara S","year":"1995","journal-title":"Nippon Sanka Fujinka Gakkai Zasshi"},{"key":"bibr18-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.284.11.1417"},{"key":"bibr19-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.106.4.625"},{"key":"bibr20-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199407000-00013"},{"key":"bibr21-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1053\/sper.2002.29862"},{"key":"bibr22-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1978.00500250015003"},{"key":"bibr23-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1978.00500310072015"},{"key":"bibr24-06-01-0024.1","first-page":"323","volume":"72","author":"De Reuck J","year":"1972","journal-title":"Acta Neurol Belg"},{"key":"bibr25-06-01-0024.1","volume-title":"Pathology of Perinatal Brain Injury","author":"Rorke LB","year":"1982"},{"key":"bibr26-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(95)00149-A"},{"key":"bibr27-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(99)00010-7"},{"key":"bibr28-06-01-0024.1","first-page":"555","volume":"63","author":"Eksioglu YZ","year":"2004","journal-title":"J Neuropathol Exp Neurol"},{"key":"bibr29-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-04-01302.2001"},{"key":"bibr30-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-16-06241.1998"},{"key":"bibr31-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0953-816X.2004.03451.x"},{"key":"bibr32-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-06-02040.1998"},{"key":"bibr33-06-01-0024.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3989-03.2004"},{"key":"bibr34-06-01-0024.1","unstructured":"Folkerth RD, Haynes RL, Wang H, Developmental regulation of manganese superoxide dismutase in rat oligodendrocytes confers protection against glutathione depletion induced toxicity. 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