PATHOGENESIS OF DIENCEPHALIC LESIONS IN AN EXPERIMENTAL-MODEL OF WERNICKES ENCEPHALOPATHY

The relationship of thiamine deficiency to Wernicke's encephalopathy h as been well established. The biochemical bases and physiologic mechan isms responsible for the pathologic changes and their selective distri bution within the brain remain controversial. The present paper review s recent biochemical, histopathological and pharmacological evidence o f a glutamate-mediated excitotoxic mechanism of neuronal loss in pyrit hiamine-induced thiamine deficiency (PTD), a rat model of Wernicke's e ncephalopathy. A mechanistic model involving the unique combination of thiamine deficiency-induced impairment of energy metabolism, increase d release of histamine, and multidirectional glutamate inputs is prese nted to explain the selective vulnerability of thalamic nuclei to exci totoxic lesions in the PTD model.