4-Hydroxynonenal immunoreactivity is increased in human hippocampus after global ischemia.

Abstract

Oxidative stress and lipid peroxidation may contribute to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD) and cerebral ischemia. 4-Hydroxynonenal (4-HNE) is a toxic by-product of lipid peroxidation, and immunoreactivity to 4-HNE has been used to examine lipid peroxidation 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 hippocampus after global ischemia, and 2) whether possession of an apolipoprotein E (APOE) epsilon4 allele influenced the extent of 4-HNE immunoreactivity. 4-HNE immunoreactivity was assessed semi-quantitatively in the temporal lobe of a group of controls (n = 44) and in a group of patients who had an episode of global ischemia as a result of a cardiorespiratory arrest and subsequently died (n = 56, survival ranged from 1hr to 42 days). There was minimal cellular 4-HNE immunoreactivity in the control group. However, compared to controls, 4-HNE immunoreactivity was significantly increased in neurons (p < 0.0002) and glia (p < 0.0001) in the hippocampal formation after global ischemia. Possession of an APOE epsilon4 allele did not influence the extent of neuronal or glial 4-HNE immunostaining in the control or global ischemia group. There was a significant negative correlation between the extent of neuronal 4-HNE immunoreactivity with survival period after global ischemia (r2 = 0.0801; p < 0.036) and a significant positive correlation between the extent of glial 4-HNE immunoreactivity and survival after global ischemia (r2 = 0.2958; p < 0.0001). The data indicate a marked increase in neuronal and glial 4-HNE. This substantiates a role for lipid peroxidation in the pathogenesis of cerebral ischemia. There was no indication that APOE genotype influenced the extent of 4-HNE immunoreactivity.

• Authors: E McKracken, D I Graham, M Nilsen, J Stewart, J A Nicoll, K Horsburgh
• Journal: Brain pathology (Zurich, Switzerland) (Brain Pathol) Vol. 11 Issue 4 Pg. 414-21 (Oct 2001) ISSN: 1015-6305 [Print] Switzerland
• PMID: 11556686 (Publication Type: Journal Article)

Chemical References

• Aldehydes
• Apolipoprotein E4
• Apolipoproteins E
• 4-hydroxy-2-nonenal

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aldehydes (metabolism)
• Alleles
• Apolipoprotein E4
• Apolipoproteins E (genetics)
• Brain Ischemia (genetics, metabolism, pathology)
• Cell Membrane (metabolism, pathology)
• Female
• Genotype
• Heart Arrest (complications)
• Hippocampus (metabolism, pathology, physiopathology)
• Humans
• Immunohistochemistry
• Lipid Peroxidation (genetics)
• Male
• Middle Aged
• Nerve Degeneration (genetics, metabolism, pathology)
• Neuroglia (metabolism, pathology)
• Neurons (metabolism, pathology)
• Oxidative Stress (genetics)
• Survival Rate