Choroid plexus dysfunction: The initial event in the pathogenesis of Wernicke's encephalopathy and ethanol intoxication
MetadataShow full item record
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.p. dose of glucose in thiamin-deficiency, an effect that was attenuated by prior MK801 and preceded the published onset of exacerbation of motor incoordination and elevation of brain glutamate derivatives; or (ii) a single i.p. dose of ethanol in thiamin-sufficiency, an effect that was proportional to the blood alcohol concentration and preceded the published onset of signs of intoxication. In contrast to the BCSFB, the BBB remained intact throughout the 90 minutes period of these experiments. Conclusions: In both ethanol intoxication and thiamin-deficient glucose metabolism, BCSFB impairment exposes the CSF and hence the brain extracellular fluid to neuroactive substances from the blood. CP impairment is the earliest detected event in both these animal models; and explains the paraventricular location of WE neuropathology and why WE is associated with, but not dependent on, alcoholism. Copyright © 2008 by the Research Society on Alcoholism.
Showing items related by title, author, creator and subject.
Alaei Shahmiri, Fariba (2012)Chronic diseases, such as cardiovascular disease and diabetes, are the leading causes of morbidity and mortality worldwide. Recent studies have shown that in addition to diabetes mellitus, non-diabetic degrees of fasting ...
The impact of thiamine supplementation on blood pressure, serum lipids and C-reactive protein in individuals with hyperglycemia: A randomised, double-blind cross-over trialAlaei-Shahmiri, F.; Soares, Mario; Zhao, Y.; Sherriff, Jill (2015)Background: The adverse effects of hyperglycemia may be potentiated when it is accompanied with hypertension and dyslipidemia. This study assessed the effects of high dose thiamine on blood pressure, serum lipids and ...
High-Dose Thiamine Supplementation Improves Glucose Tolerance in Hyperglycemic Individuals: a Randomized, Double-Blind Cross-Over TrialShahmiri, F.; Soares, Mario; Zhao, Y.; Sherriff, Jillian (2013)Purpose: To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism. Methods: Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 ...