INCREASED EXPRESSION OF IL-1-BETA CONVERTING-ENZYME IN HIPPOCAMPUS AFTER ISCHEMIA - SELECTIVE LOCALIZATION IN MICROGLIA

Although the interleukin-1 beta converting enzyme (ICE)/CED-3 family o f proteases has been implicated recently in neuronal cell death in vit ro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this ques tion, we examined the in vivo expression of one of these genes, Ice, a fter global forebrain ischemia in gerbils. Using RT-PCR and Western im munoblot techniques, we detected an increase in the mRNA and protein e xpression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CAI neurons within 2 d after i schemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 n euronal death is maximal. In nonischemic brains, ICE-like immunoreacti vity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunoreactivity w as not altered in these neurons. ICE-like immunoreactivity, however, w as observed in microglial cells in the regions adjacent to the CA1 lay er as early as 2 d after ischemic insult. The increase in ICE-like imm unoreactivity was robust at 4 d after ischemia, a period that correlat es with the DNA fragmentation observed in hippocampal homogenates of i schemic brains. These results provide the first evidence for the local ization and induction of ICE expression in vivo after ischemia and sug gest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.