Zur Entstehung von mehrkernigen Riesenzellen bei der experimentell-induzierten und spontanen Krabbeschen Krankheit (Globoid Cell Leukodystrophy)

Abstract

Introduction Krabbe's disease is a rare progressive disease occurring in infancy. It represents an inborn error of sphingolipid metabolism. The morbid anatomy of the central nervous system is characterized by severe, diffuse demyelination, astrocytic gliosis, and the presence of globoid cells. Globoid cells, i. e., PAS-positive, often multinucleated giant cells, are demonstrable only within the brains of children affected by Krabbe's disease.Though the problem of the origin of this cell type has been discussed in detail, there is no agreement wether globoid cells are transformed mesenchymal cells or glial cells. Material and Methods Experimental investigations were performed on inbred rats, approximately 130 to 200 g each, by an intracerebral injection of galacto-cerebrosides. Single rats were sacrificed after a pulse-labeling by 3H-thymidine at different days following cerebroside injection. For demonstration of the possible hematogenous origin of experimentally induced globoid cells 3H-thymidine continuously was given to the healthy partner of an irradiated parabiotic pair of rats in order to search for labeled blood-derived globoid cells within the brain of the other parabiotic rat which received cerebrosides by intracerebral injection some days before. - Moreover, the non-specific esterases were demonstrated in order to compare the enzymatic activity of peripheral blood monocytes and globoid cells. Histological investigations were performed on brain tissue of two children affected by Krabbe's disease. By simultaneous and successive demonstration of PAS-reactivity of cells which could be identified by microglial, oligodendroglial, and astroglial silver impregnation technic as well as by another astroglial stain we tried to find out which type of cells could be the precursor cell of globoid elements. Moroever, the naphthol-AS-D-chloroacetate esterase was demonstrated. Results and Discussion Using the animal model by pulse-labeling a low rate of locally proliferating, PAS-positive (globoid) cells could be observed. After a long-term survival typical globoid cell formations could be observed within the spleen of these animals as an indication of their mesenchymal relationship. Using the parabiosis-model we could demonstrate that nuclei of mononuclear, binuclear, and multinuclear PAS-positive cells - demonstrable in the damaged brain tissue - are derived from circulating blood cells. As distinct activity of non-specific esterases was demonstrable within the cytoplasm of these cells we supposed that the experimentally induced globoid cells were mainly derived from blood monocytes. The blood monocytes built up multinuclear giant cells obviously by fusion. By histological-histochemical studies using brain tissue of spontaneous Krabbe's disease two main cell types could be identified which contained PAS-positive material: (1) astrocytes, which obviously are the precursors of the typical multinucleated giant (globoid cells; (2) mesenchymal cells, which are the precursors of PAS-positive mononuclear or binuclear perivascular and leptomeningeal cells. As a consequence of these observations we concluded: experimentally induced and spontaneous Krabbe's disease are not comparable when studying cytokinetic problems of globoid cells. Moreover, galacto-cerebrosides obviously are able to induce giant cell formation by stimulating either mesenchymal or neuroectodermal elements. Two types of reaction mechanisms have been discussed: the type of foreign-body reaction in one (experimentally induced) case and a specific reaction type stimulated by an altered function in the other (spontaneous) case.