Brain ischemia and reperfusion produce profound protein synthesis alterations, the extent and persistence of which are dependent on the nature of the ischemia, the brain region, the cell layer within a region, and the particular proteins studied. After transient ischemia, most brain regions recover their protein synthesis capability; however, recovery in the selectively vulnerable areas is poor. It is unknown whether this phenomenon itself provokes or is a consequence of the process of neuronal death.

Protein synthesis suppression during ischemia is due to energy depletion, but this is quickly reversed upon recirculation. Reperfusion does not appear to damage DNA or transcription mechanisms, although there are changes in the profile 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 synthesized messenger RNAs appear to accumulate in the nucleus; this alteration in RNA handling could reflect disruption at any of several steps, including posttranscriptional processing, nuclear pore transport, cytoskeletal binding, or formation of the translation initiation complex. Another mechanism that may be responsible for protein synthesis suppression during late reperfusion is progressive membrane destruction, with consequent shifts in the concentration of ions crucial for ribosomal function.

Protein synthesis suppression after ischemia likely involves a progression of multiple mechanisms during reperfusion. Although the recent work reviewed here offers new insight into the potential mechanisms disrupting protein synthesis, detailed understanding will require further investigation.