White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain.

• 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.

Nyckelord

Animals

Antioxidants

pharmacology

Ascorbic Acid

metabolism

Asphyxia

Brain

embryology

pathology

Dehydroascorbic Acid

analogs & derivatives

Electron Spin Resonance Spectroscopy

Female

Free Radicals

Glucose

metabolism

Glutathione Peroxidase

metabolism

Lactic Acid

metabolism

Lectins

metabolism

Oxygen

metabolism

Pregnancy

Pregnancy

Animal

Reactive Oxygen Species

Regression Analysis

Reperfusion Injury

Risk

Sheep

Superoxide Dismutase

metabolism

Time Factors

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)