We report temporal profiles of cytoplasmic proteolysis and genomic DNA cleavage after
cerebral ischemia of different severity in gerbils. Global forebrain
ischemia by bilateral common carotid artery occlusion for 5 min with reperfusion, severe unilateral hemispheric
ischemia by unilateral common carotid artery occlusion for 30 min with reperfusion, and complete
ischemia by
decapitation were used. The hippocampus was examined for proteolysis by using immunohistochemistry for
microtubule-associated protein 2, DNA cleavage by using in situ nick-end labelling, and nuclear morphology by
Hematoxylin staining. During evolution of delayed neuronal death after transient forebrain
ischemia, loss of the immunoreaction for
microtubule-associated protein 2 occurred almost in parallel with DNA cleavage in the CA1 region. In contrast, disappearance of the immunoreaction for
microtubule-associated protein 2 was much faster than genomic DNA cleavage after unilateral hemispheric
ischemia and reperfusion. The
microtubule-associated protein 2 immunoreactivity was completely lost before development of changes in nuclear morphology or DNA cleavage after complete
ischemia. The present study demonstrated the differences between
necrosis and delayed neuronal death, but the nuclear morphology in the latter was not exactly the same as seen in apoptosis. Some elements of both necrotic and apoptotic machineries may work following transient
ischemia, and the degree of ischemic insult may determine the character of cell death process.