Choroid plexus dysfunction: the initial event in the pathogenesis of Wernicke's encephalopathy and ethanol intoxication.

Background: In both acute ethanol intoxication and in thiamin deficient glucose metabolism, previous studies have detected blood-brain barrier (BBB) and/or blood-CSF-barrier (BCSFB) impairment but were unable to assess their significance in relation to other changes in the brain.

Methods: Contrast-enhanced, magnetic resonance imaging (MRI) was used to detect and time any impairment of the BBB or BCSFB in rats given an acute ethanol load or in rats made thiamin deficient to the point of mild ataxia and then given an acute glucose load.

Results: The BCSFB at the choroid plexus (CP) was impaired within 10 minutes by either (i) a single i.

Glutamate export at the choroid plexus in health, thiamin deficiency, and ethanol intoxication: review and hypothesis.

Introduction: The earliest observed effect in the pathogenesis of experimental Wernicke's encephalopathy and of ethanol intoxication in rats is impairment of the blood cerebrospinal fluid (CSF) barrier at the choroid plexus (CP). For an explanation, these observations direct attention to the role of the CP in maintaining glutamate homeostasis in the CSF.

Methods: Characteristics of the CP epithelium (CPE) are reviewed, focusing on its role in removal of glutamate from the CSF and its potential for impairment by ethanol oxidation or by thiamin-deficient glucose oxidation.

Thiamin nutrition and catalysis-induced instability of thiamin diphosphate.

Thiamin (vitamin B1) is required in animal diets because it is the precursor of the enzyme cofactor, thiamin diphosphate. Unlike other B vitamins, the dietary thiamin requirement is proportional to non-fat energy intake but there is no obvious biochemical reason for this relationship. In the present communication we show for two enzymes that the cofactor undergoes a slow destruction during catalysis, which may explain the interdependence of thiamin and energy intakes.

Quantitative description of the interaction between folate and the folate-binding protein from cow's milk.

A detailed study has been carried out on the dependence of folate binding on the concentration of FBP (folate-binding protein) at pH 5.0, conditions selected to prevent complications arising from the pre-existing self-association of the acceptor. In contrast with the mandatory requirement that reversible interaction of ligand with a single acceptor site should exhibit a unique, rectangular hyperbolic binding curve, results obtained by ultrafiltration for the FBP-folate system required description in terms of (i) a sigmoidal relationship between concentrations of bound and free folate and (ii) an inverse dependence of affinity on FBP concentration.

Dietary interactions influence the effects of bovine folate-binding protein on the bioavailability of tetrahydrofolates in rats.

The newborns of mammals have a high folate demand, yet obtain adequate folate nutrition solely from their mothers' milk despite its low folate content. Milk folate is entirely bound by an excess of folate-binding protein (FBP), prompting speculation that FBP may affect the bioavailability of the limited folate supply. Previous research has shown that FBP-bound folic acid is more gradually absorbed, thereby reducing the peak plasma folate concentration and preventing loss into the urine.

Tetrahydrofolates are greatly stabilized by binding to bovine milk folate-binding protein.

The dietary supply of folates and their measurement are both affected, potentially, by the instability of some folates. Labile folates appear to be stabilized by binding to folate-binding protein (FBP); this paper reports measurements of that stabilization. The degradation rates of the very labile tetrahydrofolate (H(4)folate) and moderately labile 5-methyltetrahydrofolate (5-CH(3)H(4)folate) were measured with the compounds free or bound to either soluble or immobilized bovine milk FBP.