title: White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain.
abstract: Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.
authors.affiliation: Department of Physiology, University of Göteborg, 40530 Göteborg, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Welin
authors.forename: Mats
authors.initials: M
authors.lastname: Sandberg
authors.forename: Anna
authors.initials: A
authors.lastname: Lindblom
authors.forename: Pernilla
authors.initials: P
authors.lastname: Arvidsson
authors.forename: Ulf A
authors.initials: UA
authors.lastname: Nilsson
authors.forename: Ingemar
authors.initials: I
authors.lastname: Kjellmer
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism; D001237:Asphyxia; D001921:Brain / Q000196:embryology* / Q000473:pathology*; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D017382:Reactive Oxygen Species; D012044:Regression Analysis; D015427:Reperfusion Injury; D012306:Risk; D012756:Sheep; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D037102:Lectins; D017382:Reactive Oxygen Species; D019344:Lactic Acid; C000820:semidehydroascorbic acid; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005947:Glucose; D001205:Ascorbic Acid; D010100:Oxygen; D003683:Dehydroascorbic Acid