DOSE-RELATED EFFECTS OF CYCLOHEXIMIDE ON DELAYED NEURONAL DEATH IN THE GERBIL HIPPOCAMPUS AFTER BILATERAL TRANSITORY FOREBRAIN ISCHEMIA

Degeneration of dendrites followed by punctate chromatin condensation in the CA1 area of the hippocampus is a characteristic of delayed neur onal death following bilateral forebrain ischemia. The effects of the protein synthesis inhibitor cycloheximide on delayed neuronal death fo llowing 20 min of bilateral forebrain ischemia were examined in the ge rbil hippocampus at the 4th day of reperfusion. Low doses of cyclohexi mide beginning 10 min after ischemia (1.0 mu g/g body weight in saline followed by 1.0 mu g/g every 24 h) reduced the number of dying cells in the CA1 area, whereas high doses (2.0 mu g/g, followed by 1.0 mu g/ g every 12 h) increased the number of dying cells. No effects were see n when a single dose of cycloheximide was injected 1 h before ischemia . These results indicate that the effects of cycloheximide are dose-de pendent, low does reduce, high doses increase cell death. These findin gs also indirectly suggest that protein synthesis may play a role in t he extent of delayed neuronal death. Some involved proteins could be h eat shock proteins, which are induced after ischemia and had been corr elated with increased resistance to injury. However, changes of heat s hock immunoreactivity in the postischemic hippocampus were not seen in the present study following cycloheximide injection.