Summary: Regional protein synthesis was investigated in the rat brain during long-term recovery from insulin induced hypoglycemia with 30 min of cerebral electrical silence, At various time intervals up to 14 days after glu cose replenishment, animals received a single dose of L [3,5-3 H]tyrosine and were killed 30 min later. Brains were processed for autoradiography using the stripping film technique, Although hypoglycemia sufficiently severe to cause cessation of EEG activity leads to almost complete inhibition of amino acid incorporation in all "vulnerable" forebrain structures (cerebral cortex, hippocampus, cau doputamen), autoradiographs revealed a very specialized sequence with differential posthypoglycemic restoration of biosynthetic activity in certain neuronal cell types. Three major subpopulations could be distinguished: Neu rons that fully regained their protein synthetic capacity within 6 h following hypoglycemia (cortical neurons of layer III-VI, large neurons in the caudoputamen, CA 3 and CA4 pyramidal neurons, the majority of granule cells Although hypoglycemia is a global insult, its ef fects on the brain are regionally different. This het erogeneity applies to changes in glucose consump tion, blood flow, energy homeostasis, protein syn thesis, and neuronal cell death. Application of the [ 1 4 C]deoxyglucose technique to hypoglycemic "coma" (defined by us as hypoglycemia of suffi cient severity to cause cessation of spontaneous EEG activity) showed a striking heterogeneity in glucose consumption, with low values in the neo cortex, hippocampus, and caudoputamen and high values in the brains tern and cerebellum (Abdul Rahman and Siesjo, 1980
42of the dentate gyrus) seemed to escape neuronal necrosis.Prolonged impairment of protein synthesis with only par tial restoration during the early posthypoglycemic re covery period (CAl neurons, most small-to medium sized neurons of the caudoputamen) carried an increased risk of permanent cell damage. The large majority of these neurons, however, showed full recovery of protein synthesis as late as 7 days after hypoglycemia. Neurons with complete lack of amino acid incorporation after 6 h of recovery (granule cells at the crest of the dentate gyrus, small neurons of the dorsolateral caudoputamen) never resumed protein synthesis, regressed, and died. These studies in conjunction with morphological analysis indicate that the sequential recovery of protein synthesis reflects the extent to which neuronal populations are at risk during severe hypoglycemia. Key Words: Autora diography-Cerebral protein synthesis-Hypogly cemia-Selective vulnerability.zation during severe hypoglycemia, these data dem onstrate interregional differences in glucose avail ability. In addition, the blood flow response to hy poglycemia is regionally different both during hypoglycemia and in the recovery phase (Abdul Rahman et aI. , 1980). While many regions lose vas cular autoregulation during hypoglycemia and be come hypoperfused at very moderate degrees of ar terial hypotension, others...