Apoptosis in the Nervous System in Experimental Allergic Encephalomyelitis

We report here for the first time the occurrence of apoptosis of cells in the spinal cord in experimental allergic encephalomyelitis (EAE), an autoimmune, T-cell-mediated demyelinating disease. Four different forms of EAE were studied in the Lewis rat: (i) acute EAE induced by inoculation with whole spinal cord and adjuvants; (ii) acute EAE induced by inoculation with myelin basic protein (MBP) and adjuvants; (iii) acute EAE induced by the passive transfer of MBP-sensitized spleen cells; (iv) chronic relapsing EAE induced by inoculation with whole spinal cord and adjuvants followed by treatment with low-dose cyclosporin A. Cells undergoing apoptosis were recognized at light and electron microscopy by the presence of either crescentic masses of condensed chromatin lying against the nuclear envelope or rounded masses of uniformly dense chromatin. They were found in both the white and grey matter of the spinal cord in all 4 forms of this disease. Although it was not possible to identify definitively the types of cells undergoing apoptosis, the size and location of some of the affected cells suggested that they were oligodendrocytes. As there is now a large body of evidence that T-cell-induced target cell death takes the form of apoptosis, it is attractive to hypothesize that oligodendrocyte apoptosis is occurring in EAE as a result of oligodendrocyte-directed T-cell cytotoxicity. However, other apoptotic cells were located within the myelin sheath, meninges and perivascular spaces and were clearly not oligodendrocytes but were most likely blood-derived mononuclear cells. The sparsity of their cytoplasm and the absence of phagocytosed material suggested that they were mainly lymphocytes rather than macrophages. Apoptosis has been shown to be involved in deleting autoreactive T-cells during the normal development of tolerance. Thus apoptotic deletion of myelin/oligodendrocyte-specific lymphocytes in the central nervous system in EAE might explain both the subsidence of inflammation and the acquisition of tolerance in this autoimmune disease

An electron microscopic study of giant cytosegresomes in acute liver injury due to heliotrine

Large, PAS-positive globules that develop in the cytoplasm of the liver parenchymal cells of rats poisoned with the pyrrolizidine alkaloid heliotrine were shown to have a heterogeneous structure when examined with the electron microscope. Some represent segregated areas of cytoplasmic degradation. Others do not contain remnants of organelles and are probably derived from endocytosis vacuoles. Large, composite bodies consisting of various combinations of homogeneous vacuoles and fragments of partially degraded cytoplasm were commonly seen. Many had clearly arisen by accretion of their diverse components in sequential, discrete steps. The findings are in accord with histochemical studies indicating that the globules are lysosomal in nature. Occasionally, small dense bodies were observed in the process of fusing with large vacuoles. This suggests that the globules acquire at least some of their digestive enzymes from pre-existing lysosomes

An electron microscopic study of liver cell necrosis due to albitocin

Liver cell necrosis produced in rats by injection of the triterpenoid glycoside albitocin was studied with the electron microscope. Coagulative necrosis was of two distinct types. The first was characterized by the presence of clumps of calcium-associated, electron-opaque granules in the matrix of mitochondria, the changes closely resembling those described in necrosis due to various other toxins. However, in the second, clumps of matrix granules were absent and the appearances were like those seen in ischaemic necrosis and in in vitro autolysis. It is probable that this second type of necrosis resulted from sinusoidal obstruction, which followed the development of the first type of necrosis in the peripheral parts of the lobules. Mitochondria1 abnormalities provided the best indication of the development of coagulative necrosis, but the findings cast doubt on the importance of calcium accumulation within mitochondria as a causative factor in the initiation of necrosis. Shrinkage necrosis involved cellular condensation followed by fission into multiple, membrane-bounded cytoplasmic fragments. Some of these were ingested by parenchymal cells and histiocytes. Others probably underwent a process akin to coagulative necrosis