The proposed project consists of an analysis of lesions induced by implantation of antiglycolipid IgM antibody-secreting hybridoma cells into adult rat spinal cord dorsal columns. This procedure results in development of a focal demyelination with sparing of axons, similar to the plaques of demyelination seen in MS. The model will be used to examine the role of surviving oligodendrocyte precursors within the lesion and the role of glial cell migration from remote sources in bringing about remyelination. The principal investigator will examine the immunopathology of the lesions in correlation with electrophysiological findings and with changes in axolemmal sodium channel distribution as the lesion evolves in order to assess the functional consequences of """"""""subtle"""""""" structural damage in myelinated nerve fibers. Implantation of the same hybridomas into neonatal animals produces characteristic dysmyelination resulting from intercalation of IgM between myelin lamellae as they develop, resulting in wide-spaced myelin with a period 2X or 3X normal. Sheaths of this kind occur in MS and in paraproteinemias. The principal investigator will follow changes in these """"""""expanded"""""""" sheaths with time in order to obtain additional information about the stability of this abnormal form of myelin, about regulation of myelin sheath thickness and about the site of growth of CNS myelin sheaths.
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