Effect of Chronic Hypernatremic Dehydration and Rapid Rehydration on Brain Carbohydrate, Energy, and Amino Acid Metabolism in Weanling Mice

Abstract

This is a study of the effects of chronic hypernatremic dehydration and rehydration on carbohydrate, energy, and amino acid metabolism in the brains of weanling mice. Chronic hypernatremic dehydration induced by 4 days of water deprivation and salt loading was associated with severe weight loss (no other observed clinical effects), increased brain Na+ levels, and a decreased brain water content. Changes in the concentrations of brain glucose, glycolytic and citric acid cycle metabolic intermediates, and phosphocreatine were compatible with reduced cerebral metabolic rate. In adaptation to chronic hypernatremia, there was a significant increase in the content of the measured brain amino acids. Rapid rehydration over a 4-h period with 2.5% dextrose in water returned plasma Na+ levels and brain Na+ and water contents to normal. After rehydration, metabolites were altered in a manner consistent with increased fluxes through the glycolytic pathway and citric acid cycle; the brain glycogen content almost tripled. Brain taurine and glutamine levels were not lowered by rehydration, and the total content of the measured amino acids in brain was still significantly higher than in controls. We speculate that these metabolic perturbations may relate to the development of cerebral edema and seizures or coma following rapid rehydration of humans with chronic hypernatremic dehydration.

myo-Inositol: A Newly Identified Nonnitrogenous Osmoregulatory Molecule in Mammalian Brain

“…This increase was roughly equal to that found in chronically hypernatremic adult rats (1 9) and was quantitatively similar to the adaptive increases in levels of amino acids in these same animals (10). Rapid rehydration of the hypernatremic mice returned the plasma Naf concentration to normal but had no effect on the elevated brain myo-inositol content.…”

“…During adaptation to chronically increased or decreased plasma Nar levels, levels of amino acids in the brains of young mice increased or decreased, respectively, to maintain osmotic equilibrium and to limit the loss or gain of water in brain (10,11). The present data reveal similar paradoxic changes in the content of myo-inositol in the brains of these same animals.…”

“…Changes in the cerebral levels of myo-inositol (and amino acids) seen in chronic hyper-and hyponatremia are not merely a reflection of dehydration of the brain in one case, and edema in the other. Whereas the dry wt of the brain increased some 8 to 11 % in chronically hypernatremic mice (7, lo), myo-inositol increased 43% and levels of most amino acids increased 20 to 90% (7,9,10). Furthermore, the 88% decrease of the myoinositol concentration in chronic hyponatremia was seen without any change in the brain water content (1 1).…”

“…We have earlier reported on the effects of chronic hyper-and hyponatremia and the effect that rapid restoration of plasma Na' levels to normal has on brain water, electrolyte, carbohydrate, energy and amino acid metabolism in young mice (10,11). It was thus of interest to confirm the findings of Lohr et al (19) in the chronic hypernatremic state and to examine the effect of chronic hyponatremia, and rapid correction, on brain myoinositol levels.…”

Hypernatraemia in the Elderly Patient

“…Several ex perimental studies indicate that brain cells recover their size by the acquisition of new osmotically active solute (idiogenic osmoles) [2,27,34], The nature of idiogenic osmoles is not established, but experimental evidence indicates an increase in the cerebral content of amino-acids, in particular taurine, gluta mine, glutamate and aspartate [5,10,22,43,44], Another factor could be an increase in the osmotic activity of intracellular electro lytes due to an alteration in binding [34], Thus brain osmolality remains raised and osmotic equilibrium between extra-and in tracellular fluids is maintained.…”