Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation

Caspase activation occurs within 1h of reperfusion in discrete cell populations of the adult rat brain following transient forebrain ischemia. Based on the proximity of these cells to regions of adult neurogenesis and the known susceptibility of developing neurons to apoptosis, we tested the hypothesis that rapidly triggered post-ischemic caspase activation occurs in immature neurons or neuroprogenitor cells. Adult male Long Evans rats were injected with BrdU to label mitotic cells 1, 7, or 28 days prior to being studied. Rats were then subjected to either sham surgery or 10-min transient forebrain ischemia. At 1h after reperfusion, rats underwent perfusion fixation and brains prepared for immunohistochemical analysis. Immunolabeling for caspase-substrate cleavage, using an antibody directed at the caspase derived fragment of alpha-spectrin, was observed in discrete cell populations of the rostral dentate gyrus, dorsal striatum, extreme paramedian CA1 hippocampus, indusium gresium, olfactory tubercle, and thalamus. No cells double-labeled for caspase-substrate cleavage and BrdU at any time point after BrdU injection. Furthermore, cells immunolabeled for caspase-substrate cleavage did not double-label for markers of immature neurons (doublecortin) or progenitor cells (nestin), but did double-label for the mature neuronal marker NeuN. These results indicate that the phenomenon of rapidly triggered caspase activation in the adult rat brain after transient forebrain ischemia is specific to mature neurons and does not occur in neuroprogenitor cells or immature neurons.