Glucose loading precipitates acute encephalopathy in thiamin-deficient rats.

Abstract

A rat model of glucose-precipitated Wernicke's encephalopathy (WE) has been developed in which glucose loading (10 g/kg, i.p.) of ataxic thiamin-deficient (TD) rats induced episodes of gross neurological dysfunction and sometimes death. The acute effects of a glucose load on the neurological state of thiamin-replete control and TD rats were assessed by scoring of clinical observations and performance measured on a moving belt (MB) apparatus at 30 min intervals for 2 hr after the challenge. Glucose loading or saline treatment (2.5 mL, i.p.) had no significant behavioural or clinical consequences when administered to controls or rats fed TD diet for <21 days. Glucose loading of ataxic rats fed TD diet for 28-35 days precipitated episodes of gross ataxia and signs of advanced neurological dysfunction (e.g. loss of righting reflex and hyperexcitability) leading to significant increases in the Ataxia (p<0.05) and Advanced Sign (p<0.05) scores within 2 hr after the challenge. Simultaneously, the performance of these animals on the MB decreased 10-fold. Regular glucose challenges significantly increased the rate of progression of disease in TD rats when compared with untreated TD rats. This model may be useful for the further investigation of the pathogenesis of WE at the molecular level.