Regional glucose and β-Hydroxybutyrate use by developing rat brain

Rates of glucose and d-β-hydroxybutyrate use were determined in five brain regions of 20-day-old rats. The regions studied were cerebral cortex, thalamus, striatum, cerebellum, and brain stem. The tracers for determining rates of substrate use were [³H]fluorodeoxyglucose and [3-¹⁴C]-d-β-hydroxybutyrate. Two or five minutes after isotope administration the animals were sacrificed in a 6-kW, 2450-MHz focused microwave device. Ten minutes prior to isotope administration the animals were injected intraperitoneally with normal saline or DL-β-hydroxybutyrate (10mmol/kg). Blood d-β-hydroxybutyrate levels averaged 0.21 μmol/ml in saline-injected and 3.13 μmol/ml in hyperketonemic rats. Rates of glucose utilization were significantly heterogeneous between regions in both groups: thalamus > cerebral cortex ≥ striatum > brain stem > cerebellum. These rates were 20-35% lower in hyperketonemic rats. Rates of d-β-hydroxybutyrate use varied significantly between regions only in the saline group, with the brain stem rate being significantly lower than that in cortex or cerebellum. Regional rates of d-β-hydroxybutyrate use did not correlate significantly with regional rates of glucose use in either the saline or the hyperketonemic groups. Regional rates of glucose use were strongly and positively correlated between conditions, as were regional rates of d-β-hydroxybutyrate use. Thus, in 20-day-old rats, the regional heterogeneity of brain glucose use is similar to that in adult rats. d-β-Hydroxybutyrate use is much less regionally heterogeneous. When brain regional rates of d-β-hydroxybutyrate use are increased seven- to ninefold in acute hyperketonemia, there are compensatory decreases in regional rates of glucose use sufficient to keep regional rates of energy production unchanged.