Pathogenesis of diencephalic lesions in an experimental model of Wernicke's encephalopathy.

The relationship of thiamine deficiency to Wernicke's encephalopathy has been well established. The biochemical bases and physiologic mechanisms responsible for the pathologic changes and their selective distribution within the brain remain controversial. The present paper reviews recent biochemical, histopathological and pharmacological evidence of a glutamate-mediated excitotoxic mechanism of neuronal loss in pyrithiamine-induced thiamine deficiency (PTD), a rat model of Wernicke's encephalopathy. A mechanistic model involving the unique combination of thiamine deficiency-induced impairment of energy metabolism, increased release of histamine, and multidirectional glutamate inputs is presented to explain the selective vulnerability of thalamic nuclei to excitotoxic lesions in the PTD model.