Effects of Cilostazol on learning and recalling abilities and caspase-3 expression after global cerebral ischemia-reperfusion in rats

Objective To explore the effects of Cilostazol on learning and recalling abilities and caspase-3 expression after global cerebral ischemia-reperfusion in rats.Methods Transient global cerebral ischemia was induced by four-vessel occlusion in Sprague-Dawley(SD) rats,which were randomly divided into the sham-operation group(n=8×1),the model group(n=8×7) and the Cilostazol-treatment group(n=8×7).Rats in the treatment group received two oral administrations of cilostazol at 6 h and 2 h before global cerebral ischemia,then they were given cilostazol every 24 h.Rats in other groups were given the same volume of 30% dimethyl sulfoxide.Rats in the model group and the treatment group were decapitated at 6,12,24,48,72 h,5 d and 7 d after 10 min cerebral ischemia.Then the expression of caspase-3 in the CA1 region of the hippocampus was determined by immunohistochemistry.The other 24 rats were randomly divided into 3 groups: the shamoperation group(n=8),the ischemia-reperfusion group(n=8) and the treatment group(n=8).Learning and recalling abilities of rats at 7 d after global ischemia-reperfusion were determined by the Morris water maze.Results Caspase-3 was scarely expressed in the sham-operation group,while it increased at 6 hours,peaked at 72 hours,and deceased nearly to the normal level at day 7 in the model group;mean positive caspase-3 cells in the CA1 region were obviously lower in 48,72 h,5 d and 7 d subgroups of the treatment group than those in the model group(P0.05). Within 5 days,Escape Latency(EL) was significantly longer in the ischemia-reperfusion group and the treatment group than in the sham-operation group(P0.01,P0.05 respectively);within 4 days,Escape Latency(EL)was significantly shorter in the treatment group than that in the ischemia reperfusion group(P0.01);whereas on day 5,no significant differences were found in the two groups. Conclusions Cilostazol can effectively inhibit the increase of caspase-3 levels, which may be one mechanism of its increasing learning and recalling abilities of rats.