We assessed the expression of several genes encoding pro-apoptotic cysteine proteases similar to interleukin-1 beta converting enzyme (ICE) and nematode Ced-3 in association with delayed neuronal death (DND) after transient forebrain ischemia in Mongolian gerbil. The levels of the two species of Nedd2 mRNA concomitantly increased about two-fold in the whole forebrain at 3-6 h after 10-min ischemia and declined to the basal level by 24 h. In situ hybridization revealed that the Nedd2 gene was up-regulated in some neuronal populations in CA1 and CA3 regions of the hippocampus. In contrast, expression of ICE, CPP32/Yama/Apopain, and TX/ICErelll did not change within 48 h. These observations raise the possibility that up-regulation of Nedd2 in the vulnerable neurons may contribute to the proteolytic processes preceding the manifestation of apoptosis and/or necrosis after ischemic insult.