Combination of early and delayed SPET imaging using technetium-99m ethyl cysteinate dimer immediately after local intra-arterial thrombolysis.

The aim of this study was to investigate the prognostic utility of post-treatment technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission tomography (SPET) for predicting ischemic tissue outcome in cases involving embolic middle cerebral artery occlusion treated with local intra-arterial thrombolysis. We examined twenty-five patients with a moderately ischemic area determined using pretreatment technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) SPET, and with complete recanalization within 6 h. Post-treatment 99mTc-ECD SPET studies, consisting of scanning for 0.5-6.5 min (early scan) and 15-21 min (delayed scan) after tracer injection, were performed immediately after thrombolysis. The extent of the affected area outlined on pretreatment 99mTc-HMPAO SPET was used for the post-treatment early and delayed 99mTc-ECD SPET images, and the AR/CE ratio (ratio of affected regional activity to cerebellar activity) was calculated. The washout index of 99mTc-ECD in the affected area was also calculated by dividing the difference between the AR/CE ratio in the early and delayed images by the AR/CE ratio in the early image. Twelve patients without infarction or with small subcortical/basal ganglial infarction, ten with medium or large cortical infarction, and three with hemorrhage were identified by follow-up computed tomography. Although the AR/CE ratio in post-treatment early 99mTc-ECD SPET images was significantly higher in the hemorrhagic group than in the cortical infarction group, this value did not differentiate the reversible ischemia group from either the cortical infarction or the hemorrhagic group. The AR/CE ratio in post-treatment delayed 99mTc-ECD SPET images statistically differentiated the reversible ischemia group from both the cortical infarction and the hemorrhagic group. However, the difference between the cortical infarction and hemorrhagic groups was not statistically significant. The washout index of 99mTc-ECD statistically differentiated all three groups. This study demonstrated that a combination of early and delayed 99mTc-ECD SPET imaging performed immediately after thrombolysis predicts ischemic tissue outcome.

Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis.

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.