Role of glutamate receptors in periventricular leukomalacia

Periventricular leukomalacia is a form of white-matter injury that occurs in the setting of either primary or secondary hypoxia-ischemia in the premature infant. Hypoxia-ischemia induces increases in cerebral extracellular glutamate levels, thereby activating glutamate receptors on a variety of cell types within the white matter. 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 leukomnalacia.