THE EFFECT OF GLOBAL-ISCHEMIA AND RECIRCULATION OF RAT-BRAIN ON PROTEIN-SYNTHESIS IN-VITRO

Transient cerebral ischemia causes long-lasting inhibition of protein synthesis despite recovery of energy metabolism. We investigated the q uestion if this inhibition is due to the formation of a suppression fa ctor which interferes with the function of the protein synthesizing ma chinery. For this purpose rats were submitted to 20 minutes four vesse l-occlusion followed by recirculation times from 30 minutes to 7 days. Post-mitochondrial supernatant (PMS) from various brain regions was a dded to a self-contained, cell-free rabbit reticulocyte translational system, and the effect on in vitro protein synthesis was assessed by m easuring C-14-leucine incorporation over a duration of 45 minutes. PMS prepared at the end of ischemia from hippocampus, striatum and cerebe llum inhibited in vitro protein synthesis by 40% - 60% but there was o nly a minor inhibition by PMS from cerebral cortex. During post-ischem ic recirculation cortical PMS transiently induced inhibition of in vit ro protein synthesis by 30% but this effect gradually disappeared with in one week. The inhibition caused by PMS from hippocampus, striatum a nd cerebellum was not reversed during recirculation and still amounted to about 40% after 7 days. Inhibition of in vitro protein synthesis c ould be blocked by heating PMS to 100 degrees C, indicating that the s uppressor factor is a protein. The comparison of the in vitro effect o f postischemic PMS with previously described in vivo inhibition of pro tein synthesis demonstrates that the here observed suppressor factor i s not able to explain the overall disturbance of protein synthesis in vivo. However, the inhibitory potency of this factor after as long as 7 days after recirculation points to an ongoing pathological process, the importance of which remains to be clarified.