The relationship between enzyme activity and neuroglia in the prodromal and demyelinating stages of cyanide encephalopathy in the rat

Abstract

The neuroglial and enzyme changes in the prodromal stage of experimentally produced demyelinating disease were studied in the rat. Twenty-five animals were injected subcutaneously with NaCN 5 days a week for 3 weeks. At sacrifice selected blocks from the brain were stained cytologically for oligodendroglia and microglia and histochemically for adenosine triphosphatase (ATPase), diphosphopyridine nucleotide reductase (DPNH2) and lactic dehydrogenase. Necrotic lesions develop during the first few days of cyanide injections and demyelinating lesions usually appear from about the 14th day of injection onwards. The demyelinating lesions are characterized by early oligodendroglial proliferation followed by demyelination with the axons relatively preserved. The number of enzymatically-active oligodendrocytes in the corpus callosum increases during the progress of cyanide encephalopathy even before the appearance of demyelinating lesions. In addition to this increase in number, the staining intensity and size of their mitochondria also increases. The number of active cells continues to increase in the early demyelinating lesion but subsequently declines. Increases in enzyme activity are not seen in necrotic lesions. A study of average diameters in areas of the corpus callosum show that oligodendrocytes undergo hypertrophy and hyper-plasia in the pre-demyelinating phase of cyanide encephalopathy and acute swelling in the early stages of the demyelinating lesion. Microglia do not show activation until a definite necrotic or advanced demyelinating lesion develops. Activated and gitter forms of microglia are found only in the edge of the early necrotic lesion but throughout the demyelinating lesion. Hypertrophic and multinucleate forms of astrocytes are seen in early necrotic lesions while hypertrophic and clasmatodendritic forms of astrocytes are present in the edge of older demyelinating lesions. Increased oxidative enzyme activity of astrocytes is seen in both necrotic and demyelinating lesions. The observations indicate that in experimentally induced demyelination in the rat oligodendroglial changes precede the onset of demyelination. It is suggested, therefore, that such changes occur in the prodromal stage of the human lesion and that oligodendroglial activity at the edge of the multiple sclerosis plaque is a primary feature of the disease.