Postischaemic changes in protein synthesis in the rat brain: effects of hypothermia.
Protein synthesis, measured as [14C]-leucine incorporation into proteins, was studied in the normothermic rat brain following 15 min of transient cerebral ischaemia and 1 h, 24 h and 48 h of recirculation, and in the hypothermic (33 degrees C) brain following 1 h and 48 h of recirculation. Ischaemia was induced by bilateral common carotid occlusion combined with hypotension. Following normothermic ischaemia, incorporation of [14C]-leucine was depressed by 40-80% at 1 h of recirculation in all brain regions studied. At 48 h postischaemia, incorporation returned to normal or above normal levels in the inner layers of neocortex, the CA3 region, the striatum and the dentate gyrus, while in the outer layers of neocortex and in the hippocampal CA1 region the incorporation was persistently decreased by 26% and 40% respectively. At 24 and 48 h postischaemia, protein synthesis in the CA1 region and the striatum could be attributed to proliferating microglia. Intra-ischaemic hypothermia ameliorated the persistent depression of protein synthesis in the CA1 region at 48 h postischaemia, and a two-fold increase compared to the normothermic group was observed both in the CA1 region and the striatum. In the cortex, eucaryotic initiation factor 2 activity transiently decreased at 30 min postischaemia. In animals subjected to intra-ischaemic hypothermia, the eucaryotic initiation factor 2 activity was reduced by 50% of control at 30 min of recirculation compared with 77% in normothermic animals. We conclude that the postischaemic depression of protein synthesis is in part caused by a decrease in eucaryotic initiation factor 2 activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Bergstedt
K
K
Laboratory for Experimental Brain Research, Lund University, Lund Hospital, Sweden.
Hu
B R
BR
Wieloch
T
T
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007930:Leucine / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D012358:RNA, Transfer, Met / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002250:Carbon Radioisotopes; D015852:Eukaryotic Initiation Factor-2; D009419:Nerve Tissue Proteins; D012358:RNA, Transfer, Met; D007930:Leucine