TI - Possible mechanisms involved in the down-regulation of translation during transient global ischaemia in the rat brain . AB - The striking correlation between neuronal vulnerability and down-regulation of translation suggests that this cellular process plays a critical part in the cascade of pathogenetic events leading to ischaemic cell death . There is compelling evidence supporting the idea that inhibition of translation is exerted at the polypeptide chain initiation step , and the present study explores the possible mechanism/s implicated . Incomplete forebrain ischaemia ( 30 min ) was induced in rats by using the four-vessel occlusion model . Eukaryotic initiation factor ( eIF ) 2 , eIF4E and eIF4E -binding protein (4E-BP1) phosphorylation levels , eIF4F complex formation , as well as eIF2B and ribosomal protein S6 kinase ( p70 ( S6K ) ) activities , were determined in different subcellular fractions from the cortex and the hippocampus [the CA1-subfield and the remaining hippocampus ( RH ) ] , at several post-ischaemic times . Increased phosphorylation of the alpha subunit of eIF2 ( eIF2 alpha ) and eIF2B inhibition paralleled the inhibition of translation in the hippocampus , but they normalized to control values , including the CA1-subfield , after 4--6 h of reperfusion.eIF4E and 4E-BP1 were significantly dephosphorylated during ischaemia and total eIF4E levels decreased during reperfusion both in the cortex and hippocampus , with values normalizing after 4 h of reperfusion only in the cortex . Conversely , p70 (S6K) activity , which was inhibited in both regions during ischaemia , recovered to control values earlier in the hippocampus than in the cortex.eIF4F complex formation diminished both in the cortex and the hippocampus during ischaemia and reperfusion , and it was lower in the CA1-subfield than in the RH , roughly paralleling the observed decrease in eIF4E and eIF4G levels . Our findings are consistent with a potential role for eIF4E , 4E-BP1 and eIF4G in the down-regulation of translation during ischaemia.eIF2 alpha , eIF2B , eIF4G and p70 (S6K) are positively implicated in the translational inhibition induced at early reperfusion , whereas eIF4F complex formation is likely to contribute to the persistent inhibition of translation observed at longer reperfusion times .