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Cerebral glucose transport and metabolism in preterm human infants
W J Powers1, J L Rosenbaum, C S Dence
1Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Insights
Early human brain glucose transport shows similar glucose transporter affinity but reduced capacity in preterm infants. Cerebral glucose uptake is linked to plasma glucose, unlike overall brain glucose metabolism.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Limited data exists on early human cerebral glucose transport and metabolism during development.
- Understanding these processes is crucial for assessing brain development in preterm infants.
Purpose of the Study:
- To measure cerebral blood flow (CBF), cerebral glucose transport (CTXglc), and cerebral metabolic rate for glucose (CMRglc) in preterm human infants.
- To estimate the kinetic parameters (Kt and Tmax) of glucose transport in the developing human brain.
- To compare these parameters with those of the mature brain.
Main Methods:
- Positron emission tomography (PET) was used to measure CBF, CTXglc, and CMRglc in six preterm infants (25-34 weeks gestational age) aged 4-7 days.
- Michaelis-Menten constants (Kt and Tmax) were calculated using CTXglc and plasma glucose concentrations.
- Correlation analyses were performed between CMRglc, CTXglc, and plasma glucose levels.
Main Results:
- Mean CMRglc was 8.8 mumol/100g/min and did not correlate with plasma glucose.
- CTXglc significantly correlated with plasma glucose (r=0.836, P=0.038).
- Estimated Kt was 6.0 mumol/mL, similar to mature brains, indicating comparable glucose transporter affinity.
- Estimated Tmax was 32.6 mumol/100g/min, approximately one-third to one-half of mature brain values, suggesting reduced transporter capacity.
Conclusions:
- The affinity of glucose transporters in the developing human brain is similar to that of mature brains.
- However, the maximal transport rate (Tmax) is significantly lower in preterm infants, indicating fewer available transporters.
- Cerebral glucose transport, but not overall metabolism, is sensitive to plasma glucose levels in early development.
Abstract:
Few data regarding early developmental changes in cerebral (blood-to-brain) glucose transport (CTXglc) and CMRglc are available for humans. We measured CBF, CTXglc, and CMRglc with positron emission tomography at 4 to 7 days of life in six preterm human infants whose estimated gestational age was 25 to 34 weeks. The Michaelis-Menten constants Kt and Tmax were estimated from CTXglc and the calculated cerebral capillary plasma glucose concentration. Mean CMRglc was 8.8 mumol 100 g-1 min-1. The CMRglc did not correlate with plasma glucose concentration (r = .315, P = .543), whereas CTXglc showed a significant correlation with plasma glucose concentration (r = .836, P = .038). Estimation of the Michaelis-Menten constants from the best fit to the measured data produced values of Kt = 6.0 mumol mL-1 and Tmax = 32.6 mumol 100 g-1 min-1. These values for Kt in the developing human brain are similar to those that have been reported for the mature brain of adolescent and adult humans and adult nonhuman primates, indicating the affinity of the glucose transport protein for D-glucose is similar. However, Tmax is approximately one third to one half of the comparable values for mature brain, indicating a reduced number of available luminal transporters.