The present study examined the cytopathological changes within diencephalon of a rat model of
Wernicke's encephalopathy and determined whether administration of
thiamine at various intervals after onset of neurological signs can arrest or reverse the cytopathological process. Electron microscopic examination of the brains from animals sacrificed at four progressively severe stages of
pyrithiamine-induced
thiamine deficiency (PTD) revealed neurocytopathological changes identical to those that have been described in
glutamate-induced excitotoxic lesions. These degenerative changes occurred in gelatinosus (Ge) and anteroventral ventrolateral (AVVL) nuclei at an early symptomatic stage and in the ventroposterolateral (VPL), ventroposteromedial (VPM), and ventrolateral (VL) nuclei at slightly later stages of PTD. Light microscopic evaluation of separate groups of PTD rats administered
thiamine at each of the same four neurologic stages and allowed to recover for 1 week demonstrated that
thiamine treatment is more effective when administered at earlier stages. However, Ge, AVVL, and VPL nuclei sustain severe damage even when
thiamine is administered prior to acute
neurologic signs. Furthermore, pathologic changes in the mammillary and several midline intralaminar nuclei begin after
thiamine administration and reinstitution of
thiamine-replete diet to animals in more severe stages of
thiamine deficiency. These and other recent findings suggest that excitotoxic and possibly apoptotic mechanisms may mediate neuronal degeneration in the PTD rat model of
Wernicke's encephalopathy, and that multiple factors conducive to excitotoxicity may act in concert to produce this syndrome.