Edematous necrosis in thiamine-deficient encephalopathy of the mouse.

Acute encephalopathy was produced in the adult male Swiss mouse by pyrithiamine injection in conjunction with a thiamine-deficient diet. The condition of some mice was reversed within 24 hours by a treatment of a high dose of thiamine. The lesions occurred selectively in the thalamus, pontine tegmentum, and mammillary body and were manifested by hemorrhage and edematous necrosis consisting of severe edema of astrocytes, myelin sheaths, and neuronal dendrites. Before thiamine treatment, these degenerative changes were not associated with any mesenchymal reaction. At 48 and 96 hours after thiamine treatment, these edematous changes persisted. Fat-laden macrophages appeared in the lesion. Some axons showed Wallerian-type degeneration. After three weeks of thiamine treatment, macrophages became thin and rod-shaped. Wallerian-type degeneration and myelin edema persisted. The oligodendrocytes and astrocytes were hypertrophic. These lesions of thiamine-treated encephalopathy of the mouse closely resembled the non-hemorrhagic lesions of human Wernicke encephalopathy. Mice which were concomitantly-induced with hyperglycemia and encephalopathy showed no significant differences in clinical and morphologic manifestations from the encephalopathic mice with normal blood sugar levels. Vascular permeability to horseradish peroxidase was increased only slightly at the initial stage, but was reversed in the mice which clinically responded quickly to thiamine treatment. Occasionally, persistent increase of permeability was seen in 21-day-old lesions. These findings suggested that, in thiamine-deficient encephalopathy, both nervous and vascular components in the brain were involved and that the morphologic manifestations of the nervous component were far more extensive than those of the blood vessels.