Isoprostanes,
neuroprostanes, isofurans, and neurofurans have all become attractive
biomarkers of oxidative damage and lipid peroxidation in brain tissue.
Asphyxia and subsequent reoxygenation cause a burst of
oxygen free radicals.
Isoprostanes and isofurans are generated by
free radical attacks of esterified
arachidonic acid.
Neuroprostanes and neurofurans are derived from the peroxidation of docosahexanoic
acid, which is abundant in neurons and could therefore more selectively represent oxidative
brain injury. Newborn piglets (age 12-36 h) underwent
hypoxia until the base excess reached -20 mmol/L or the mean arterial blood pressure dropped below 15 mm Hg. They were randomly assigned to receive
resuscitation with 21, 40, or 100%
oxygen for 30 min and then ventilation with air. The levels of
isoprostanes, isofurans,
neuroprostanes, and neurofurans were determined in brain tissue (ng/g) isolated from the prefrontal cortex using gas chromatography-mass spectrometry (GC/MS) with negative ion chemical ionization (NICI) techniques. A control group underwent the same procedures and observations but was not submitted to
hypoxia or
hyperoxia.
Hypoxia and reoxygenation significantly increased the levels of
isoprostanes, isofurans,
neuroprostanes, and neurofurans in the cerebral cortex. Nine hours after
resuscitation with 100%
oxygen for 30 min, there was nearly a 4-fold increase in the levels of
isoprostanes and isofurans compared to the control group (P=0.007 and P=0.001) and more than a 2-fold increase in neuroprostane levels (P=0.002). The levels of
neuroprostanes and neurofurans were significantly higher in the piglets that were resuscitated with supplementary
oxygen (40 and 100%) compared to the group treated with air (21%). The significance levels of the observed differences in
neuroprostanes for the 21% vs 40% comparison and the 21% vs 100% comparison were P<0.001 and P=0.001, respectively. For neurofurans, the P values of the 21% vs 40% comparison and the 21% vs 100% comparison were P=0.036 and P=0.025, respectively. Supplementary
oxygen used for the
resuscitation of newborns increases lipid peroxidation in brain cortical neurons, a result that is indicative of oxidative brain damage. These novel findings provide new knowledge regarding the relationships between oxidative
brain injury and
resuscitation with
oxygen.