Role of apoptosis following cerebral hypoxia-ischemia in immature and older rats

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Sidhu, Ranjinder S.
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In the present study, we sought to investigate the age dependence of apoptosis during cerebral hypoxia-ischemia and the effectiveness of a specific caspase-3 inhibitor. To determine the role of apoptosis in mature and immature brain following an episode of cerebral hypoxia-ischemia, cell types were examined under light microscopy and were quantified morphologically. Evidence of punctate chromatin condensation, indicative of apoptosis, was greater in immature brain than in older brain. Role of caspase-3 was examined by measuring caspase-3 activity and caspase-3 protein using Western blotting techniques. Caspase-3 activity was significantly increased in animals exposed to hypoxia-ischemia, with a 3-fold greater caspase-3 activity in immature than older brain. In addition active caspase-3 was detectable 18hr post-hypoxia in 4 wk olds and at 4hr and 18hr following hypoxia in 1 wk olds. In the last study, animals were treated with a caspase-3 specific inhibitor in order to determine its effectiveness as a neuroprotective agent. Doses of 1.5-6$\mu$g/g body weight of z-DEVD-fmk I.P. were not effective in reducing infarction. (Abstract shortened by UMI.)