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 neuronal death following bilateral forebrain ischemia. The effects of the protein synthesis inhibitor cycloheximide on delayed neuronal death following 20 min of bilateral forebrain ischemia were examined in the gerbil hippocampus at the 4th day of reperfusion. Low doses of cycloheximide beginning 10 min after ischemia (1.0 microgram/g body weight in saline followed by 1.0 microgram/g every 24 h) reduced the number of dying cells in the CA1 area, whereas high doses (2.0 micrograms/g, followed by 1.0 microgram/g every 12 h) increased the number of dying cells. No effects were seen when a single dose of cycloheximide was injected 1 h before ischemia. These results indicate that the effects of cycloheximide are dose-dependent, low doses reduce, high doses increase cell death. These findings also indirectly suggest that protein synthesis may play a role in the extent of delayed neuronal death. Some involved proteins could be heat shock proteins, which are induced after ischemia and had been correlated with increased resistance to injury. However, changes of heat shock immunoreactivity in the postischemic hippocampus were not seen in the present study following cycloheximide injection.
Tortosa
A
A
Unidad de Neuropatología, Servicio de Anatomía Patológica, Hospital Príncipes de España, Universidad de Barcelona, Spain.
Rivera
R
R
Ferrer
I
I
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D016548:Prosencephalon / Q000098:blood supply*
D008869:Microtubule-Associated Proteins; D003513:Cycloheximide