The CA1 pyramidal neurons in the hippocampus are selectively vulnerable to transient ischemic damage. In experimental animals, the CA1 pyramidal neurons undergo cell death several days after brief forebrain ischemia. It remains, however, unknown whether this delayed neuronal death is necrosis or apoptosis. To investigate the degenerating processes of the CA1 pyramidal neurons in gerbil hippocampus after brief ischemia, lysosomal and nuclear alterations in the cells were examined using immunocytochemistry, in situ nick-end labeling, and Southern blotting. By light and electron microscopy, immunoreactivity for cathepsins B, H, and L, representative lysosomal cysteine proteinases, increased in the CA1 pyramidal neurons 3 d after ischemic insult, which showed cell shrinkage. By morphometric analysis, the volume density of cathepsin B-positive lysosomes markedly increased 3 d after ischemic insult, while that of autophagic vacuole-like structures also increased at this stage, suggesting that cathepsin B- immunopositive lysosomes increasing in the neurons after ischemic insult are mostly autolysosomes. Nuclei of the CA1 neurons were nick- end labeled by biotinylated dUTP mediated by terminal deoxytransferase 3 and 4 d after ischemic insult, but not in the prior stages. Simultaneously, dense chromatin masses appeared in nuclei of the neurons. By Southern blotting, laddering of DNA occurred only in CA1 hippocampal tissues obtained 4 d after ischemic insult. Confocal laser scanning microscopy demonstrated that the fragmented DNA in the CA1 pyramidal layer was phagocytosed by microglial cells. The results suggest that delayed death of the CA1 pyramidal neurons after brief ischemia is not necrotic but apoptotic.

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We investigated changes in locomotor activity, passive avoidance task performance, and hippocampal CA1 neurons induced by cerebral ischemia in Mongolian gerbils to examine the relation between these behavioral changes and CA1 neuronal damage. Spontaneous locomotor activity was measured using the open field method before and 1, 3, 7, 14, or 28 days after 1- to 5-minute occlusion of the bilateral common carotid arteries. Locomotor activity after the second episode of 5-minute ischemia was also measured at 1-month intervals. The passive avoidance task was performed 7 or 28 days after induced ischemia. Histopathological changes in CA1 neurons after ischemia were assessed. Locomotor activity was increased 1 and 3 days after induced ischemia but not 14 and 28 days later. When the gerbils were again subjected to 5-minute ischemia 1 month after the initial 5-minute induced ischemia, locomotor activity even 1 day later was significantly increased. In contrast, passive avoidance impairment depended on the duration of ischemia, as determined 7 and 28 days after induced ischemia. Hippocampal CA1 neuronal damage was progressive, that is, changes in CA1 neurons were apparent even 1 day after 5 minutes of induced ischemia, and the CA1 neurons disappeared 7 days after 5 minutes of ischemia. Passive avoidance impairment after ischemia is related to damage of CA1 neurons. Changes in locomotor activity after induced ischemia do not seem to be linked to CA1 neuronal damage.

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