Internucleosomal DNA cleavage involved in ischemia-induced neuronal death

Pyramidal neurons of the hippocampal CA1 are known to be particularly vulnerable to transient ischemia resulting in "delayed neuronal death". Recent studies using aurintricarboxylic acid suggested that ischemia- or excitotoxin-induced neuronal death should share intracellular mechanisms in common with apoptosis. It is, however, unclear about involvement of endonucleases. Here using a transient (5 min) forebrain ischemia model in gerbils, we found that internucleosomal DNA fragmentation developed between 48 and 54 hr recirculations, accompanied with simultaneous or slightly preceding destruction of microtubule-associated protein 2. These results suggest that endonucleases, maybe activated by elevated intracellular Ca2+, play an important role in delayed neuronal death as well as in apoptosis.