Distribution of hydroxynonenal-modified proteins in the kainate-lesioned rat hippocampus: Evidence that hydroxynonenal formation precedes neuronal cell death

Decomposition of lipid peroxides gives rise to a wide range of aldehydes. 4 -Hydroxyalkenals and in particular 4-hydroxynonenal (HNE) are often the mos t toxic products. Frequently, it is unclear at which stage in the tissue in jury process HNE is formed, i.e., is it a late stage or an early stage in w hich HNE contributes to subsequent cell death? The present study was carrie d out using an antibody to HNE-modified proteins to elucidate the time cour se and distribution of HNE in the lesioned hippocampus after kainate inject ions. HNE was absent from normal neurons, but dense staining to HNE was obs erved in degenerating neurons after kainate injection. The increase in HNE staining occurred as early as 1 d postinjection, at a time when there was n o histological evidence of cell death. HNE immunoreactivity was observed in the degenerating CA1 and CA3 fields at 3 d and 1 week postinjection, but w as confined to a cluster of neurons at the edge of the degenerating CA fiel ds, at 2 and 3 weeks postinjection. These observations suggest that HNE for mation is an early event after this tissue injury, and may contribute to la ter cell death. (C) 2000 Elsevier Science Inc.