Activation of caspase-activated deoxyribonuclease and neuroprotective effect of caspase-3 inhibitor after focal cerebral ischemia-reperfusion injury

Caspase-3 is a key enzyme to execute apoptosis and may be cause internucleosomal DNA fragmentation in ischemic neurons. However, whether caspase-3 inhibitor can directly inhibit caspase-3–dependent deoxyribonuclease activity and prevent neuronal apoptosis following cerebral ischemic is unknown. In this study, we detected the caspase-3 and CAD protein, as well as the frequencies of neuronal apoptosis in both model control group (DMSO injection) and treatment group (Ac-DEVD-CHO injection) after focal cerebral ischemia-reperfusion in rats. Our data showed that caspase-3 and CAD protein were detectable, and apoptotic-like neuronal death occurred following cerebral ischemic in both groups. However, these results obtained were inhibited by Ac-DEVD-CHO in treatment group as compared with model control group. Taken together, these data further support that the pathway of caspase-3–dependent CAD activity and neuronal apoptosis is an important mechanism in ischemic neuronal injury, and Ac-DEVD-CHO has the neuroprotective effect to a certain degree.   Key words: Caspase-3, caspase-activated deoxyribonuclease, Ac-DEVD-CHO, apoptosis, cerebral ischemia.