Acute application of an interleukin-1 beta-converting enzyme-specific inhibitor delays axotomy-induced motoneurone death

When performed during the postnatal period, lesioning of the facial nerve induces apoptotic death of facial motoneurones. Several lines of evidence indicate that the ICE proteases family, the mammalian homologues of Ced-3, are positive effecters of this process. In order to determine whether these proteases are involved in axotomy-induced cell death in vivo, we applied a peptide inhibitor of ICE, WAD-CHO, to the lesioned facial nerve of 2-day-old mice. The effect of WAD-CHO on motoneurone death was tested using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) method, which labels apoptotic DNA breaks in situ. Our results show that acute application of YVAD-CHO can partially delay motoneurone death since 32% fewer TUNEL-labelled motoneurones were observed in treated mice. These results indicate that ICE or ICE-like proteases may be involved in the cell death processes induced by an axotomy in vivo.