Roles of caspase-3 in neuron apoptosis following cerebral ischemia/reperfusion in the hippocampus of rats

Objective To investigate the roles of Caspase 3 in neuron apoptosis following cerebral ischemia/reperfusion in the rat hippocampus. Methods A model of rats with global ischemia induced by occlusion of the four vessels according to the method by Pulsinelli et al was used in this study. A total of 182 Wistar rats [(220±20) g] were divided randomly into three groups: control group ( n =14), cerebral ischemia group ( n =84), and cerebral ischemia group treated with acetyl asp glu val asp aldehyde (Ac DEVD CHO, n =84). Time points for observation included 8, 24, 48, 72, 120, and 168 h in the latter two groups. Caspase 3 activity in cytosolic extracts (S 100) of hippocampus and apoptotic neurons in hippocampus following cerebral ischemia/reperfusion were observed at the above mentioned time points, respectively. Results (1) No caspase 3 activity was detected in S 100 from the control group. In S 100 from the ischemia group, weak caspase 3 activity was detected at 8 h, but it increased gradually and peaked at 120 h, and then decreased apparently at 168 h after reperfusion. After treatment with Ac DEVD CHO following cerebral ischemia/ reperfusion, caspase 3 activity was inhibited to some extent at each time point. (2) Apoptotic cells were occasionally observed in hippocampus in the control group, but the apoptotic cells increased apparently at 24 h, peaked at 120 h, and decreased a few at 168 h after reperfusion in ischemia group. After treatment with Ac DEVD CHO following cerebral ischemia/reperfusion, apoptosis decreased to some extent at each time point (except 8 h following cerebral ischemia/ reperfusion). (3) Caspase 3 activity in S 100 from hippocampus was positively correlated with apoptotic neurons in hippocampus following cerebral ischemia/reperfusion at each time point ( r =0.9356 in ischemia group, r =0.980 0 in treatment group). Conclusion Caspase 3 may be one of the key causes resulting in neuron apoptosis in rat hippocampus after cerebral ischemia/reperfusion. It may play an important role in ischemia reperfusion brain injury.