Background: The proliferation of oligodendrocytes and their association with hypertrophic astrocytes has been previously described in resolving multiple sclerosis (MS) lesions.
Experimental design: Central nervous system lesions of different ages were examined from 9 cases of MS with clinical histories ranging from 8 weeks to 13 years and in a variety of non-MS conditions.
Results: In MS, these associations were found to occur most frequently in acute, actively demyelinating (as opposed to resolving) lesions. They also occurred, albeit rarely, in chronic active and chronic silent MS plaques and in areas showing remyelination or normal myelination adjacent to lesions. Immunocytochemistry revealed that the oligodendrocytes occurred in increased numbers and displayed enhanced reactivity for HNK-1, similar to previous studies that claimed such cells to be of recent origin. Ultrastructurally, hypertrophic astrocytes in the lesion center usually possessed no formed bundles of intermediate filaments, but rather displayed a finely granular cytoplasm. Towards the perimeter, they contained bundles of filaments and showed increased staining with anti-glial fibrillary acidic protein antibody. The interactions involved the close apposition to, and internalization of oligodendrocytes by astrocytes, between which membrane specializations occurred, suggestive of an adhesion event. Identical glial associations were also seen in various non-MS conditions. In most of the latter cases, there was evidence of central nervous system inflammation and/or destruction.
Conclusions: These observations underscore the increased frequency of the glial cell phenomenon in active MS lesions, its ubiquity in diseases of different etiologies and the need for careful scrutiny of control central nervous system tissue in assessing the specificity of phenomena attributed to MS. It is suggested that these glial associations may represent a transient protective mechanism and may be related to local cytokine production.