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Periventricular white\u2010matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia; PVL) and diffuses myelination disturbances. Recent neuroimaging studies support that the incidence of PVL is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. Factors that predispose to PVL during prematurity include hypoxia, ischemia, and maternal\u2013fetal infection. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical\u2010mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary, but not sufficient to generate PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin\u2010forming oligodendrocytes. Chemical mediators that may contribute to white\u2010matter injury include reactive oxygen species glutamate, cytokines, and adenosine. As our understanding of the pathogenesis of PWMI improves, it is anticipated that new strategies for directly preventing brain injury in premature infants will develop. MRDD Research Reviews 2006;12:129\u2013140. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrdd.20107","type":"journal-article","created":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T15:35:28Z","timestamp":1151508928000},"page":"129-140","source":"Crossref","is-referenced-by-count":279,"title":["Perinatal white matter injury: The changing spectrum of pathology and emerging insights into pathogenetic mechanisms"],"prefix":"10.1002","volume":"12","author":[{"given":"Stephen 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