抄録
Wernicke's encephalopathy-like neurological symptoms were induced in rats by thiaminedeficient diet or administration of pyrithiamine. Male S.D. rats of 4 week-old were divided into the following three groups: (1) thiamine-deficient diet+pyrithiamine treatment (PT), (2) thiaminedeficient diet alone (TD) and (3) control diet. On the 18th day of the feeding the mean thiamine concentration in the blood was 0.56 μg/dl in the thiamine-deficient group while it was 26.76. μg/ dl in the control. Weight gain decreased remarkably on the 27 th day of the feeding in the thiamine-deficient group (P<0.001). From this time on, the intraperitoneal injection of pyrithiamine has been carried out. The injected dose was 50. μg/100g body weight/day in PT. Neurological symptoms, such as ataxic gait and convulsion, appeared within 7 days. In TD, the change in posture (arched back) appeared within 5 weeks, followed by neurological symptoms as in PT.
The slices of the cerebral cortex, 0.3mm thick, were prepared from the rats immediately after the appearance of the neurological symptoms. Then an aliquot of the slices were placed in Warburg vessels containing the incubating medium with 0.2μCi [U-14C] glucose. Oxygen uptake and 14CO2, liberation were determined by 90 minute incubation at 37... After the incubation, the contents of the vessels were homogenized altogether and the concentrations of lipids, glycogen, glucose, amino acids, lactate and pyruvate were determined chemically as well as radiologically after the modification of Gaitonde and others.
By comparing PT with the control, the following results were obtained; significant increase in the incorporation of 14C into lactate (P<0.001); significant increase in the concentration of it (P<0.05) ; significant increase in the concentration of amino acids (P<0.01) ; increase in the concentration of lipids; decrease in the incorporation of 14C into lipids and amino acids (statistically not significant); no significant changes in oxygen uptake, glucose and pyruvate.
On the other hand, the measured values in TD were intermediate between those of PT and the control. These results may suggest that the thiamine deficiency, induced by pyrithiamine, exerts inhibitory effects not only on glucose metabolism, but also on lipids and amino acids metabolism in the cerebral cortex.
Microscopically, TD and PT showed small hemorrhage and spongy degeneration in the middle pons and the pontine tegmentum, in addition to extracellular edema in the cerebral cortex. In PT, small hemorrhage and pallor of the cerebellar white mater were also found. In PT, vacuolation of glial foot process and irregular myelin sheath were electron-microscopically noted.
