SUPPRESSION OF PROTEIN-SYNTHESIS IN THE REPERFUSED BRAIN

Background: Brain ischemia and reperfusion produce profound protein sy nthesis alterations, the extent and persistence of which are dependent on the nature of the ischemia, the brain region, the cell layer withi n a region, and the particular proteins studied. After transient ische mia, most brain regions recover their protein synthesis capability; ho wever, recovery in the selectively vulnerable areas is poor. It is unk nown whether this phenomenon itself provokes or is a consequence of th e process of neuronal death. Summary of Review: Protein synthesis supp ression during ischemia is due to energy depletion, but this is quickl y reversed upon recirculation. Reperfusion does not appear to damage D NA or transcription mechanisms, although there are changes in the prof ile of transcripts being made. Similarly, purified ribosomes isolated from reperfused brains can make the normal repertoire of proteins and heat-shock proteins. However, during early reperfusion, newly synthesi zed messenger RNAs appear to accumulate in the nucleus; this alteratio n in RNA handling could reflect disruption at any of several steps, in cluding posttranscriptional processing, nuclear pore transport, cytosk eletal binding, or formation of the translation initiation complex. An other mechanism that may be responsible for protein synthesis suppress ion during late reperfusion is progressive membrane destruction, with consequent shifts in the concentration of ions crucial for ribosomal f unction. Conclusions. Protein synthesis suppression after ischemia lik ely involves a progression of multiple mechanisms during reperfusion. Although the recent work reviewed here offers new insight into the pot ential mechanisms disrupting protein synthesis, detailed understanding will require further investigation.