In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose uptake increased disproportionately to cerebral oxygen uptake, and the cerebral oxygen to glucose uptake ratio was 4.2. The accumulated excess glucose uptake during 6 minutes of activation amounted to 2.4 micromol/g. Activation was terminated by closure of the sheltering box. In the postactivation period, the cerebral oxygen to glucose uptake ratio rose to a maximum of 6.4. This response is exactly opposite to the excess cerebral glucose uptake observed during activation.

Background and Purpose-It has previously been shown that activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR glc ) in excess of cerebral oxygen uptake (CMRO 2 ).Our purpose was to investigate the influence of ␤-adrenergic blockade with propranolol on the activation-induced uncoupling of cerebral glucose and oxygen metabolism. Methods-Using awake rats, we determined the cerebral arteriovenous differences of oxygen [(aϪv) and lactate [(aϪv) lac ] both under baseline conditions and during activation. The molar ratio between CMRO 2 and CMR glc , the oxygen-glucose index (OGI), was calculated. Results-Without ␤-adrenergic blockade, activation decreased the (aϪv) O2 but not the (aϪv) glc , reducing the OGI from 6.1 during baseline conditions to 4.0 under activation (PϽ0.01). The (aϪv) O2 decreased, indicating that the ratio CBF/CMRO 2 had increased. Under baseline conditions, a slight flux of lactate from the brain was observed. Activation increased the arterial lactate concentration, and during this condition, the lactate flux from the brain was reversed into a slight lactate uptake. Propranolol administration did not change the behavior of the animals during activation. After administration of propranolol, baseline values were unaffected, but ␤-adrenergic blockade totally abolished the activation-induced uncoupling of (aϪv) O2 from (aϪv) glc , because both remained constant with an unchanged OGI. The unchanged (aϪv) O2 indicates that CBF remained unchanged compared with CMRO 2 . Conclusions-␤-Adrenergic

In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of b-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated is not known. Alterations in several parameters may possibly explain the increase in CBF and the resetting of the relation between CBF and cerebral metabolism. To study this phenomenon further, we measured global CBF and global cerebral metabolism with the Kety-Schmidt technique in the wakeful rat before and during infusion of ketone bodies. During acute hyperketonemia (average concentration of b-hydroxybutyrate: 6 mmol/L), global CBF increased 65% from 108 to 178 mL/ 100 g min and the cerebral metabolic rates for both oxygen and glucose remained constant. This resetting of the relation between CBF and cerebral metabolism could not be explained by alterations in blood pH or arterial CO 2 tension. By measuring cerebral intracellular pH by 31 P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions.