LATE-ONSET LIPID-PEROXIDATION AND NEURONAL CELL-DEATH FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA IN RAT-BRAIN

We previously reported that iron deposition was seen in the cerebral c ortex and hippocampal CA1 area late after transient forebrain rated by four-vessel occlusion in rats. Iron deposition in the hippocampal CA1 area was coupled with delayed pyramidal cell death, while that in the cerebral cortex was not accompanied by neuronal death or atrophy unti l 6 months after ischemia. Iron is involved in the formation of free r adicals, thus contributing to lipid peroxidation. To elucidate whether this iron has deleterious effects on neurons, we investigated changes in the levels of lipid peroxidation and resulting neuronal damage in this ischemia model. The level of malondialdehyde plus 4-hydroxynonena l as major decomposition products of lipid peroxidation, monitored for 6 months beginning just after 30 min of transient forebrain ischemia, was significantly increased in the cerebral cortex at 6 months, and i n the striatum from 1 week to 6 months compared to that in sham-operat ed controls. Histological changes were also examined up to 1 year afte r reperfusion by immunohistochemical methods. In contrast with the hip pocampus and striatum, the cerebral cortex did not develop severe neur onal cell death and atrophy until 1 year after the ischemic insult. We showed that lipid peroxidation took place not only immediately after ischemia-reperfusion but also late after the ischemic insult in region s where iron was deposited, and we showed that neuronal cell death in the cerebral cortex appeared extremely late, suggesting that iron-medi ated lipid peroxidation may be of importance in some slowly progressiv e forms of neurodegeneration. (C) 1997 Elsevier Science B.V.