Developmental Modulations of Blood-Brain Barrier Permeability as an Indicator of Changing Nutritional Requirements in the Brain

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Abstract
Summary: The intracarotid injection technique has been utilized to examine blood-brain barrier function in studies of newborn (>24 h), 7, 14, 21 and 28 day-old, as well as adult rabbits. The age-related modulations in blood-brain barrier transport of adenine, arginine, choline, lactate and tryptophan were defined and demonstrated to be independent of each other. Lactic acid uptake was unusual in that the brain uptake index (BUI) was found to be greatest at 7 days postpartum. Elevated lactate uptake continues until 14 days and is then reduced. As indicated below, for all of the other metabolites examined, a maximal BUI was observed in the newborn brain and BUIs typically showed some sort of inverse relationship to animal age. The BUI of arginine is apparently halved in the first 7 days postnatally, and continues to decrease, reaching the value seen for the adult rabbit by an age of 21 days. In contrast, the brain uptake of adenine is unusual in that there appears to be a very gradual reduction in brain uptake occurring throughout the suckling period. A 3-fold decrease in the BUI of choline was observed during the first 2 wk postpartum. Tryptophan uptake undergoes a 4-fold reduction in the first 4 wk postnatally. Only minor variations in the uptakes of glucose and butanol (a reference substance which is completely cleared by brain over a wide range of blood flow rates) were observed over the range of ages examined. Therefore modulations in adenine, arginine, choline, lactate and tryptophan permeability are not attributable to blood flow alterations. Speculation: The brain uptake rates of the metabolites which gain access by way of specific carrier mediated transport mechanisms are presumed to reflect nutritional requirements of the developing brain. Thus the present study indicates that the inclusion of these metabolites (adenine, arginine, choline, tryptophan and monocarboxylic acids such as lactate) would be beneficial in clinical intravenous feeding of the neonate, to meet the apparent needs of the developing central nervous system.