It has been proposed that
reactive oxygen species and lipid peroxidation have a role in the delayed neuronal death of pyramidal cells in the CA1 region. To explore the in situ localization and serial changes of 4-hydroxy-2-nonenal-modified
proteins, which are major products of membrane peroxidation, we used immunohistochemistry of the gerbil hippocampus after transient forebrain
ischemia with or without preconditioning
ischemia. The normal gerbil hippocampus showed weak immunoreactivity for 4-hydroxy-2-nonenal-modified
proteins in the cytoplasm of CA1 pyramidal cells.
4-hydroxy-2-nonenal immunoreactivity showed no marked changes after preconditioning
ischemia. In the early period after
ischemia and reperfusion, there was a transient increase of nuclear
4-hydroxy-2-nonenal immunoreactivity in CA1 pyramidal neurons. In contrast, cytoplasmic immunoreactivity transiently disappeared during same period and then increased markedly from 8h to seven days. One week after
ischemia,
4-hydroxy-2-nonenal immunoreactivity was observed within reactive astrocytes in the CA1 region. Early nuclear accumulation of
4-hydroxy-2-nonenal in CA1 neurons may indicate a possible role in signal transduction between the nucleus and cytoplasm/mitochondria, while delayed accumulation of 4-hydroxy-2-nonenal-modified
proteins in the cytoplasm may be related to mitochondrial damage. We conclude that
4-hydroxy-2-nonenal may be a key mediator of the oxidative stress-induced neuronal signaling pathway and may have an important role in modifying delayed neuronal death.