Oligodendrocyte And Axon Pathology In Clinically Silent Multiple Sclerosis Lesions
Mews I, Bergmann M, Bunkowski S, Gullotta F, Bruck W
Mult Scler 1998 Apr;4(2):55-62
Univ of Gottingen, Dept of NeuroPathology, Germany
PMID# 9599334; UI# 98261700
Oligodendrocyte and Axon pathology was studied in 11 autopsy cases of clinically silent Multiple Sclerosis.
A total of 54 Lesion, either DeMyelinated or late ReMyelinated, were distributed through the whole Brain and Spinal Cord with 39% of the lesions located in PeriVentricular areas.
Determination of Axon density revealed an average reduction of 64% and 59% in DeMyelinated and ReMyelinated lesions with an extreme variation between different plaques and cases.
Oligodendrocytes were identified by ImmunoCytoChemistry for Myelin Oligodendrocyte Glycoprotein (MOG) and in situ hybridization for ProteoLipid Protein (PLP) mRNA.
Oligodendrocytes were almost completely lost in DeMyelinated lesions; ReMyelinated lesions revealed preservation of a considerable number of Oligodendrocytes within the lesions.
At the border between plaques and the periplaque White Matter, similar Oligodendrocyte numbers as in ReMyelinated lesions were found.
Different factors including lesion site, Axonal preservation and ReMyelination may thus contribute to the Clinical NonAppearance of Multiple Sclerosis Lesions.
The Pathology Of Multiple Sclerosis
Neurol Clin 1995 Feb;13(1):1-21
Palo Alto VA Medical Center, Laboratory Service (113), CA 94304, USA
PMID# 7739499; UI# 95257895
Multiple Sclerosis (MS) is a Chronic Neurologic disease characterized in early phases by a Cellular Immune Response and later by multiple areas of DeMyelination or plaques in the Central Nervous System (CNS) White Matter.
The clinical manifestations of the disease are highly variable, but probably are related to the extent of breakdown of the Blood-Brain Barrier associated with Inflammation in the acute phase, and with the extent of DeMyelination in the chronic phase.
The initiating events of MS are not known, but current hypotheses include Immune Responses to an initiating Viral infection and AutoImmune responses to CNS Myelin Antigens.
Both Inflammatory and CNS resident cells contribute to the ImmunoPathology of the disease. Chronic Lesions are characterized by Glial scarring and depletion of both Oligodendrocytes and Axons.
Patterns Of OligodendroGlia Pathology In MS
Ozawa K, Suchanek G, Breitschopf H, Bruck W, Budka H, Jellinger K, Lassmann H
Brain 1994 Dec;117 ( Pt 6):1311-22
Austrian Academy of Sciences, Research Unit for Experimental NeuroPathology, Wien, Austria
PMID# 7820568; UI# 95120491
Patterns of Inflammation, DeMyelination and Oligodendrocyte pathology were studied in acute Multiple Sclerosis and during early and late exacerbations of Chronic Multiple Sclerosis.
Cells within lesions were identified by ImmunoCytoChemistry with markers for T-Lymphocytes, Macrophages, Oligodendrocytes and Astrocytes.
In addition, in situ hybridization for ProteoLipid Protein mRNA was used to identify Myelinating and Myelin supporting Oligodendrocytes.
Degenerating cells in the lesions were detected by DNA fragmentation in cell nuclei. The Inflammatory reaction in all three types of Multiple Sclerosis lesions was shown to be dominated by T-Lymphocytes and Macrophages.
In late Chronic Multiple Sclerosis lesions, a significant increase in the number of ImmunoGlobulin producing Plasma Cells was found in infiltrates as compared with acute and early Multiple Sclerosis Lesions.
In all three types of Multiple Sclerosis, confluent plaques of DeMyelination were found to be present:
- In acute Multiple Sclerosis, DeMyelination was found to be associated with extensive destruction of other tissue elements, including Oligodendrocytes, Astrocytes and Axons.
During early exacerbations of Chronic Multiple Sclerosis, selective DeMyelination was associated with almost complete preservation of Oligodendrocytes in the majority of cases.
In lesions developing late after onset of Multiple Sclerosis, DeMyelination generally accompanied extensive destruction and loss of Oligodendrocytes.
- But even in these destructive Lesion, a considerable number of Oligodendrocytes was preserved and at disposal therefore, for rapid ReMyelination.
- In these lesions, ReMyelination was sparse and restricted to lesional borders.
The observed patterns of cell death suggest that in some cases Oligodendrocytes, in others Myelin Sheaths are the primary target of the destructive process.
Our data indicate that the type and amount of Inflammation, De- and ReMyelination, and of tissue damage vary between different forms of Multiple Sclerosis and between different stages of the disease, possibly reflecting Different Pathogenic Mechanisms in a disease spectrum.