Glucose Availability to Individual Cerebral Structures Is Correlated to Glucose Metabolism

Summary: D-Glucose and L-leucine are transported across the blood-brain barrier (BBB) by two separate carrier-mediated facilitated diffusion mechanisms. In the awake rat there are regional differences in blood-to-brain glucose transport among the cerebral cortex, cerebellum, hippocampus, and striatum. To determine whether these are due to variations in the regional density or affinity of the glucose transporter moiety of brain capillaries or are secondary to regional tissue perfusion and capillary ar rangement characteristics, we studied (a) regional blood to-brain transport of L-leucine in awake rats; (b) regional blood-to-brain transport of both glucose and leucine under chloral hydrate anesthesia, a condition associated with altered regional brain blood now (BF) and metabo lism; and (c) regional brain vascular volume, derived from the L-glucose and inulin spaces, in both awake andWe have reported regional differences in the blood-to-brain transport characteristics of D-glu cose in awake rats . Briefly summarized, glucose influx was similar in the cerebral cortex and cerebellum over a wide range of plasma glucose concentrations (2-40 mM), despite lower blood flow (BF) to the cerebellum. The lower BF is balanced by a higher glucose ex traction fraction in the cerebellum. Because glu cose metabolic rate is lower in the cerebellum than in the cerebral cortex of awake rats (Sokoloff et al., 1977), the cerebellum is relatively oversupplied with glucose, which may explain its relative resis tance to hypoglycemia (Abdul-Rahman and Siesjo, 1980; Agardh et aI., 1981; Ratcheson et aI., 1981; Kiessling et aI., 1982). On the other hand, the Abbreviations used: BBB, blood-brain barrier; BF, blood flow; PS, permeability-surface area. 717anesthetized rats. We found the same regional differences in blood-to-brain leucine transport in awake rats as we previously described for D-glucose transport. These re gional differences in glucose and leucine transport disap pear under chloral hydrate anesthesia, as regional differ ences in BF are abolished. However, we found regional differences in the brain vascular volumes, which are evi dent in wakefulness and persist during anesthesia. These results suggest that the regional differences in blood-to brain transport are due mainly to local tissue perfusion and capillary arrangement characteristics rather than to intrinsic regional differences in the transport systems of the BBB. Key Words: Blood-brain barrier-Regional brain blood flow-Regional brain blood volume-Re gional brain capillary characteristics-Regional brain glucose and leucine transport.blood-to-brain glucose transport capacity of the hippocampus was significantly less than that of the cerebral cortex and cerebellum, which may render the hippocampus glucose deficient under condi tions associated with high glucose metabolism such as seizures. Regional differences in the blood-to brain glucose transport may be due to (a) differ ences in the density and/or affinity of the glucose transporter of regional brain capillaries; (b)...

Section: Discussionsupporting

confidence: 92%

Regional Studies of Blood—Brain Barrier Transport of Glucose and Leucine in Awake and Anesthetized Rats

LaManna

Harik

1986

“…This circumstance can arise only when the glucose transport kinetics are commensurate with glucose utilization, as demonstrated by the kinetic modeling which found similar ratios of V max /CMR Glc in white and gray matter for both models used. This result is in excellent agreement with that obtained by Hawkins et al (1983), who found a significant regional correlation between glucose influx and glucose utilization. Pan et al (2000) measured gray and white matter neuronal glucose oxidation in a similar volume of the visual cortex as in the present study using magnetic resonance spectroscopy.…”

Section: Glucose Transport Kineticssupporting

confidence: 93%

Differentiation of Glucose Transport in Human Brain Gray and White Matter

Graaf

Pan

Telang

et al. 2001

Summary:Localized 1 H nuclear magnetic resonance spectroscopy has been applied to determine human brain gray matter and white matter glucose transport kinetics by measuring the steady-state glucose concentration under normoglycemia and two levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements were simultaneously performed on three 12-mL volumes, containing predominantly gray or white matter. The exact volume compositions were determined from quantitative T 1 relaxation magnetic resonance images. The absolute brain glucose concentration as a function of the plasma glucose level was fitted with two kinetic transport models, based on standard (irreversible) or reversible MichaelisMenten kinetics. The steady-state brain glucose levels were similar for cerebral gray and white matter, although the white matter levels were consistently 15% to 20% higher. The ratio of the maximum glucose transport rate, V max , to the cerebral metabolic utilization rate of glucose, CMR Glc , was 3.2 ± 0.10 and 3.9 ± 0.15 for gray matter and white matter using the standard transport model and 1.8 ± 0.10 and 2.2 ± 0.12 for gray matter and white matter using the reversible transport model. The Michaelis-Menten constant K m was 6.2 ± 0.85 and 7.3 ± 1.1 mmol/L for gray matter and white matter in the standard model and 1.1 ± 0.66 and 1.7 ± 0.88 mmol/L in the reversible model. Taking into account the threefold lower rate of CMR Glc in white matter, this finding suggests that blood-brain barrier glucose transport activity is lower by a similar amount in white matter. The regulation of glucose transport activity at the blood-brain barrier may be an important mechanism for maintaining glucose homeostasis throughout the cerebral cortex.

“…There is now evidence that transport capacity correlates with metabolic demand for glucose both interregionally and between physiological states Hawkins et a!., 1983;Cremer, 1986). The values for the regional maximal trans port capacities reported here would allow, under normoglycaemic conditions, transport rates of ap proximately twice the corresponding metabolic rates for glucose in anaesthetized rats.…”

Section: Discussionmentioning

confidence: 99%

Regional Blood—Brain Glucose Transfer in the Rat: A Novel Double-Membrane Kinetic Analysis

Cunningham

Hargreaves²,

Pelling³

et al. 1986

Summary: Regional blood-brain glucose transfer was studied in pentobarbitone-anaesthetized rats using a pro grammed intravenous infusion technique that maintained steady levels of unlabeled (up to 55 mM) and tracer n-glucose in the circulating plasma. Regional cerebral blood flow, glucose phosphorylation rate, and tissue glu cose content were also measured under comparable con ditions. Data were analysed in terms of irreversible Mi chaelis -Menten kinetics assuming independent influx and efflux (Type I) and reversible Michaelis-Menten ki netics (Type II) across both the luminal and the abluminal membranes of the endothelial cell. The latter analysis corresponds to simple stereospecific membrane pores. The mathematical model allowed for changes in tissue glucose content and back-diffusion of tracer during the Glucose is transported across the blood-brain barrier principally by a process of facilitated diffu sion (Crone, 1965;Lund-Andersen, 1979).