Anaphase-promoting complex (APC) and its coactivator Cdh1 are required for maintaining cells in G1 phase of cell cycle in proliferating cells. Recent studies showed that Cdh1-APC was active in post-mitotic neurons, which regulates neuronal survival, differentiation, axonal growth and synaptic development. However, the possible function of Cdh1-APC in ischemic brain injury has not been determined. This study aimed to investigate changes in the activity of Cdh1-APC in hippocampus after global cerebral ischemia in rat. We found that, compared with sham group, the expression of Cdh1 in hippocampus was significantly decreased on 1 and 3 days of reperfusion in ischemia group (P < 0.05), while neuronal apoptosis were found in hippocampal CA1 region and the two downstream substrates of Cdh1-APC (SnoN and Skp2) were significantly increased after global cerebral ischemia (P < 0.05). This study demonstrates that the down-regulation of Cdh1-APC is associated with neuronal apoptosis in hippocampus following global cerebral ischemia. It brings a prospect to explore the further function of Cdh1-APC in the injured nervous system. (C) 2011 Elsevier Ireland Ltd. All rights reserved.