Regionally selective inhibition of cerebral protein synthesis in the rat during hypoglycemia and recovery.

Regional cerebral protein synthesis was investigated in anesthetized, mechanically ventilated rats during progressive insulin-induced hypoglycemia and the recovery period following glucose infusion. Polysome profiles from precomatose animals with slow wave/polyspike EEG revealed a slight reduction of polyribosomes and a concurrent increase in monoribosomes, but autoradiographs showed a pattern of L-[3-3H]tyrosine incorporation indistinguishable from that of control rats. During the initial 30 min of insulin-induced isoelectric EEG ("coma"), autoradiographs showed a selective inhibition of protein synthesis in neurons and glial cells of the hippocampus and cerebral cortex, i.e., regions with high susceptibility for the development of hypoglycemic brain damage. Basal ganglia were less affected and areas with low vulnerability (hypothalamus, brainstem, and cerebellum) exhibited a normal pattern of amino acid incorporation. Using a flooding dose of L-[1-14C]valine (7.5 mmol/kg; 15 microCi/mmol), the rate of incorporation in cerebral cortex and cerebellum was found to be reduced to 2% and 80% of control values, respectively. Inhibition of protein synthesis was paralleled by a breakdown of polyribosomes and a concomitant increase in ribosomal subunits, indicating a block in peptide chain initiation. After 90 min of isoelectric EEG all brain structures with the exception of hypothalamus and area postrema showed an almost complete lack of amino acid incorporation. Glucose infusion after a 30-min period of hypoglycemic coma led to a partial restoration of cortical and hippocampal protein synthesis. Within 70-90 min of recovery, L-[1-14C]valine incorporation into neocortical and cerebellar proteins amounted to 47% and 125% of fasted controls.(ABSTRACT TRUNCATED AT 250 WORDS)