We have previously described a rodent model of brief (30 min)
middle cerebral artery occlusion followed by reperfusion, in which
infarction develops gradually, reaching completion more than 3 days after
ischemia, accompanied by morphological, biochemical, and pharmacological evidence of apoptosis. In the present study, we tested the hypotheses that delayed administration of a
protein synthesis inhibitor would be effective in reducing tissue injury in this slowly evolving ischemic
infarction, and that efficacy of this treatment would wane with more prolonged
ischemia. Focal
cerebral ischemia was induced in Long-Evans rats by occlusion of the right middle cerebral artery.
Infarction volume was analyzed using triphenyl tetrazolium
chloride staining, and morphology was studied using
hematoxylin and
eosin stained sections. Following 30 min
middle cerebral artery occlusion and reperfusion, the core ischemic region exhibited vacuolization in the neuropil by 36 h after
ischemia, and
infarction reached full size by 7 days after
ischemia.
Cycloheximide reduced
infarct volume when given up to 6 h after
ischemia. If the duration of ischemic insult was increased to 90 min, the therapeutic window for delayed
cycloheximide was only 30 min. In permanent
middle cerebral artery occlusion,
cycloheximide was ineffective even when given prior to
ischemia onset. After mild, but not severe, ischemic insults,
cerebral infarction develops slowly and may be treatable with
protein synthesis inhibitors, even when treatment is delayed for up to 6 h after the onset of
ischemia.