Generation of lipid radicals in the hippocampus of neonatal rats after acute hypoxic-ischemic brain damage.

Free radical-mediated lipid peroxidation has been strongly suggested to be the main cause of neuronal toxicity in the rat brain, including neonatal brain damage. The primary objective of this experiment was to see if the generation of free radicals occurred in the acute phase of ischemic-hypoxic insult in neonatal rats, by electron paramagnetic resonance (EPR) spectroscopy and in vivo brain microdialysis. A spin trap agent, alpha-(4-pyridyl-N-oxide)-N-tert-butylnitrone was perfused through a probe in the hippocampus before and after hypoxia and then an analysis was performed by EPR. From the EPR analysis of spin adduct in the dialysates, we obtained the EPR spectrum of six line spectra for which the hyperfine coupling constants corresponded to those of the EPR signal from the lipoxygenase/linoleic acid (LPX/LA), a lipid radical generating system, increased transiently just after hypoxia. The results of our in vivo study show the lipid peroxidation of the neuronal membrane to progress during neonatal ischemic-hypoxic insult. We hypothesize that an increased formation of lipid radicals may participate in the cascade of reactions leading to neuronal damage in the hippocampus following ischemic-hypoxic insult in neonatal rats.