Axon reactions precede demyelination in experimental models of multiple sclerosis.
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Biomedical subjects
Publications and source records attributed to A Filchev.
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Taking into consideration that myelin phospholipids may be partially synthesized in neuronal bodies, while neurilemma readily reacts with antibodies against gangliosides by changing the properties of membrane ionic channels, the attempt was made to test the proposed assumption of the early axonal reaction in demyelinating processes in experimental models of multiple sclerosis. The models of chronic allergic encephalomyelitis in Lewis rats injected with homogenate of highly purified myelin or total brain gangliosides were used. First signs of demyelination (the destruction of intermediate dense lines) were demonstrated in the inner layers of myelin close to axon and were shown to develop synchronously with the aggregation of filamentous-tubular material in the neuroplasm. These changes are associated with significant shift of the ratio of myelin sheath thickness to axonal diameter (from 1:7-1:3 to 2:1-3:1). This swelling of myelin seems to be caused by neuroplasmic proteins aggregation, that must be accompanied by the drop in oncotic pressure and the separation of loosely-bound water fraction that may be assimilated by myelin. At light microscopic level the increase of myelin thickness is clearly observed that is in exact correspondence with the decrease in axonal diameter. The process starts with the exfoliation and swelling of the nodes of Ranvier and the incisures of myelin, which fuse after elongation, that corresponds to the total disintegration of myelin with the preservation of continuity of axon which appears to be harshly shrunken.
The relative distribution of gangliosides was determined in the serum of 37 patients with multiple sclerosis (MS) and of 30 healthy subjects. There was a significant increase of GM1 and GD1a, and a decrease of GM3 proportion in the serum of relapsing-remitting MS patients (RRMS) during their first MS attack. The RRMS patients in relapse with a long duration of the disease had a significant decrease of GM1 and an increase of GD1a portion in the serum. An increase of GD1a, one of the major brain neuron ganglioside fraction, suggested the neuron injury in the early and with a long duration RRMS. The finding of an increase of GM1, the main human myelin ganglioside, during the first MS attack in RRMS patients confirms previous evidence for the possible involvement of gangliosides in the early pathological course of demyelination in MS.
Chronic relapsing experimental allergic encephalomyelitis (CREAE) was induced in Lewis rats by inoculation with guinea-pig myelin and complete Freund's adjuvant followed by treatment with low-dose cyclosporin A. Rats were sacrificed at different phases of the disease (just before the onset of clinical signs, during the first clinical episode of CREAE and during the first recovery). Gangliosides were extracted from the brain, analysed after purification by HPTLC fractionation and quantified densitometrically. An increase of GM1, the main rat myelin ganglioside, and a decrease of GT1b, suggested to play a role in mediating the interactions between oligodendroglia and axons, were observed during the development of the CREAE. These findings indicating significant ganglioside changes in CREAE give further support to the concept concerning the involvement of gangliosides in autoimmune demyelination.
Chronic relapsing experimental allergic encephalomyelitis (CREAE) was induced in Lewis rats by inoculation with guinea-pig myelin and complete Freund's adjuvant followed by treatment with low-dose cyclosporin A. Rats were sacrified at different phases of the disease (just before the onset of clinical signs, during the first clinical episode of CREAE and during the first recovery). Gangliosides were extracted from the spinal cord, analysed after purification by two-dimensional chromatography and quantified densitometrically. An increase of GM 1, the main rat myelin ganglioside, and a decrease of GT1b, suggested to play a role in mediating the interactions between oligodendroglia and axons, were observed during the development of the CREAE. These findings indicating significant ganglioside changes in CREAE give further support to the concept concerning the involvement of gangliosides in autoimmune demyelination.
Biologically active substances (BAS) were isolated from the tissues of Fasciola hepatica L. and from F. hepatica-infected rat liver by ethanol precipitation from aqueous tissue homogenates. A marked inhibiting effect of the newly isolated BAS on hepatoma MC29 cell culture proliferation and a slight inhibiting effect of the newly isolated BAS on myeloma cell culture proliferation was found. The strongest inhibiting effect was by BAS isolated from the tissues of F. hepatica. The inhibiting effect of the BAS isolated from F. hepatica-infected liver was stronger than the effect of the BAS isolated from normal liver tissue.
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