title: 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.affiliation: Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, United Kingdom. emc27m@udcf.gla.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: McKracken
authors.forename: D I
authors.initials: DI
authors.lastname: Graham
authors.forename: M
authors.initials: M
authors.lastname: Nilsen
authors.forename: J
authors.initials: J
authors.lastname: Stewart
authors.forename: J A
authors.initials: JA
authors.lastname: Nicoll
authors.forename: K
authors.initials: K
authors.lastname: Horsburgh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism*; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006323:Heart Arrest / Q000150:complications; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D015996:Survival Rate
chemical_list: D000447:Aldehydes; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C027576:4-hydroxy-2-nonenal