Dynamic changes in glucose metabolism induced by thiamine deficiency and its replenishment as revealed by a positron autoradiography technique using rat living brain slices

Dynamic changes in the cerebral glucose metabolic rate (CMRglc) before and after thiamine replenishment were investigated in living brain slices obtai ned from pyrithiamine-treated (PT) and pair-fed control rats by use of a po sitron autoradiography technique. Fresh rat brain slices (300 mu m thick) w ere incubated with [F-18]2-fluoro-2-deoxy-D-glucose ([F-18]FDG) in oxygenat ed Krebs-Ringer solution at 36 degrees C, during which serial two-dimension al images of [F-18]FDG uptake in the slices were constructed on the imaging plates. The net influx constant (=K) of [F-18]FDG was determined by a Patl ak graphical method of the image data. Prior to thiamine pyrophosphate (TPP )-loading, the K value in the neurologically symptomatic PT was higher in a ll brain regions except the thalamus and mammillary body than the control, suggesting compensatory enhanced glycolysis. The rapid decrease in this hei ghtened net influx constant immediately after TPP-loading was surmised to b e due to activation of pyruvate oxidation with lactate as the substrate, wi th this inhibiting the glycolysis. From greater than or equal to 150 min af ter TPP-loading, the K value continued to show low values in the thalamus a nd mammillary body, which are regarded as the responsible sites for Korsako ff syndrome, whereas in all other sites recovery to control values was obse rved. These findings suggest that using this technique the quantitative eva luation of serial local changes in CMRglc from thiamine deficiency to after its replenishment may be useful in elucidating the pathophysiology and pro gnosis of Wernicke's encephalopathy. (C) 1999 Published by Elsevier Science B.V. All rights reserved.