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This review examines the evidence of a role for glutamate receptors in white-matter injury and periventricular leukomalacia. Multiple glutamate receptor subtypes exist, and these appear to play differential roles depending on cell type and time after injury. Glutamate receptors are developmentally regulated on neurons and glia, and certain subtypes are transiently overexpressed in developing rodent brain and are expressed on immature oligodendrocytes in human white matter in the premature period. Pharmacologic agents acting on glutamate receptors might represent age-specific therapeutic strategies for the treatment of periventricular leukomalacia. 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