Histopathologic ond enzyme histochemical observations of the cuprizone-induced brain edema

Abstract

The induction of status spongiosus and astrocytosis in the brains of mice by dietary administration of 0.3% cuprizone was studied sequentially by histopathological and enzyme-histochemical techniques. The study demonstrated a progressive development in the severity and distribution of the status spongiosus and astrocytosis. Edematous vacuolation of both grey and white matter was observed in a few specific brain locations as early as the 5th day of cuprizone feeding but by the 3rd week, and later, status spongiosus was severe throughout the brain. Reactive astrocytes were not apparent in the edematous brain tissue until after the 7th day of feeding, but by the 14th day reactive astrocytes were a characteristic feature of the cuprizone encephalopathy. Reactive astrocytes occurred in the areas of edema and generally paralleled the edema in severity although there were exceptions. Qualitative enzyme-histochemical studies revealed that normal astrocytes exhibited little or no oxidative enzyme activity whereas reactive astrocytes showed strong activity for the various enzymes studied. Weak glutamate dehydrogenase (GDH) activity was detected in astrocytes after only 3 days of cuprizone feeding followed, after 5 days and later, by strong activity for GDH, NAD diaphorase, and lactic dehydrogenase. Increased staining intensity for NADP diaphorase, glucose-6-phosphate dehydrogenase, and succinic dehydrogenase was observed in reactive astrocytes late in the experiment but the staining intensity for these enzymes never reached that of GDH and NAD diaphorase.