The patterns of expression of the bcl-2, bax, and bci-X genes were examined immunohistochemically in neurons of the adult rat brain before and after 10 min of global ischemia induced by transient cardiac arrest. High levels of the cell death promoting protein Bax and concomitant low levels of the apoptosis-blocking protein Bcl-2 were found in some populations of neurons that are particularly sensitive to cell death induced by transient global ischemia, such as the CA1 sector of the hippocampus and the Purkinje cells of the cerebellum. Moreover, within 0.5 to 3 hr after an ischemic episode, immunostaining for Bax was markedly increased within neurons with morphological features of degeneration in many regions of the brain. Use of a two-color staining method for simultaneous analysis of Bax protein and in situ detection of DNA-strand breaks revealed high levels of Bax immunoreactivity in many neurons undergoing apoptosis. Postischemic elevations in Bax protein levels in the hippocampus, cortex, and cerebellum were also demonstrated by immunoblotting. At early times after transient ischemia, regulation of Bcl-2 and Bcl-x protein levels varied among neuronal subpopulations, but from 3 hr on, those neurons with morphological evidence of degeneration uniformly contained reduced levels of Bci-2 and particularly Bci-X immunoreactivity. The findings suggest that differential expression of some members of the bcl-2 gene family may play an important role in determining the relative sensitivity of neuronal subpopulations to ischemia and that postischemic alterations in the expression of bax, bcl-2, and bcl-x may contribute to the delayed neuronal cell death that occurs during the repurfusion phase after a transient ischemic episode.

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The present investigation was undertaken to study the ultrastructural morphology of brain blood vessels during vasospasm following total cerebral ischemia. Global cerebral ischemia was produced in rats by compression of the cardiac vessel bundle (i.e., cardiac arrest) using a metal hook that was introduced into the mediastinum. Ischemia lasted for 10 min with blood recirculation for 6, 12 and 24 h. Rat brains were perfusion-fixed and regions from the cerebral cortex and associated leptomeningeal vessels were evaluated by scanning and transmission electron microscopy. We noted three general vasoconstrictive responses in vessels of various sizes including veins and arteries. These alterations related to the smooth muscle cell arrangement associated with each constricted vessel including a circumferential, and longitudinal arrangement, or a combination of both types. Other features in the three types of vasoconstricted vessels included thickening of the vessel basement membranes with increased endothelial microfilaments and vesicular profiles. Our studies present evidence that ischemia of 10-min duration with blood reflow for 6, 12 and 24 h produces profound and variable vasospastic changes in some but not all vessels. These vascular alterations are thought to be caused in part by vasoactive substances released both by endothelial and blood cells and by perivascular cellular elements in response to the ischemic episode.

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