Oxidative stress, brain white matter damage and intrauterine asphyxia in fetal lambs

In order to examine the role of oxidative stress in asphyxia-induced perina tal brain damage, near-term fetal lambs were subjected to umbilical cord oc clusion for approximately 60 min until fetal arterial pH diminished to less than 6.9 and base excess to less than - 20 meq/l. The levels of superoxide , hydrogen peroxide, glutathione (GSH) and thiobarbiturate-reactive substan ces (TEARS) within brain grey and white matter were determined at 72 h to c orrelate with morphological changes. Although the topography and extent of brain damage varied somewhat from case to case, ranging from focal infarcti on in grey or white matter to subtle and patchy alterations of white matter , the telencephalic white matter appeared to bear the brunt of damage as co mpared to other regions. The parietal white matter, in particular was often the seat of early pathological changes that could be seen in isolation. Th ese while matter changes were accompanied by significant increases in hydro gen peroxide and TEARS levels as compared to those in grey matter. In anoth er set of experiments, 8 different brain regions were assayed for TEARS. GS H and superoxide dismutase (SOD). A highly significant rise in the levels o f TEARS was again noted in the parietal and frontal white matter. SOD level s were higher in the frontal and parietal white matter, basal ganglia and c erebellum. Cerebral cortical and hippocampal neurons were relatively unaffe cted until accompanied by more severe damage to grey and white matter at ot her sites. These results suggest that the developing telencephalic while ma tter appears to be most vulnerable to the effects of intrauterine fetal asp hyxia and that oxidative stress may be a major contributing factor in the p athogenesis of perinatal hypoxic-ischemic encephalopathy. (C) 1999 ISDN. Pu blished by Elsevier Science Ltd. All rights reserved.