4-hydroxynonenal immunoreactivity is increased in human hippocampus after global ischemia

Oxidative stress and lipid peroxidation may contribute to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD) and cerebral i schemia. 4-Hydroxynonenal (4-HNE) is a toxic byproduct of lipid peroxidatio n, and immunoreactivity to 4-HNE has been used to examine lipid peroxidatio n in the pathogenesis of AD and ischemia. This study sought to determine 1) if there are cellular alterations in 4-HNE immunoreactivity in the human h ippocampus after global ischemia, and 2) whether possession of an apolipopr otein E (APOE) epsilon4 allele influenced the extent of 4-HNE immunoreactiv ity. 4-HNE immunoreactivity was assessed semi-quantitatively in the tempora l lobe of a group of controls (n = 44) and in a group of patients who had a n episode of global ischemia as a result of a cardiorespiratory arrest and subsequently died (n = 56, survival ranged from 1 hr to 42 days). There was minimal cellular 4-HNE immunoreactivity in the control group. However, com pared to controls, 4-HNE immunoreactivity was significantly increased in ne urons (p < 0.0002) and glia (p < 0.0001) in the hippocampal formation after global ischemia. Possession of an APOE epsilon4 allele did not influence t he extent of neuronal or glial 4-HNE immunostaining in the control or globa l ischemia group. There was a significant negative correlation between the extent of neuronal 4-HNE immunoreactivity with survival period after global ischemia (r(2) = 0.0801; p < 0.036) and a significant positive correlation between the extent of glial 4-HNE immunoreactivity and survival after glob al ischemia (r(2) = 0.2958; p < 0.0001). The data indicate a marked increas e in neuronal and glial 4-HNE. This substantiates a role for lipid peroxida tion in the pathogenesis of cerebral ischemia. There was no indication that APOE genotype influenced the extent of 4-HNE immunoreactivity.