Studies on factors accounting for remyelination in the central nervous system

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Using organotypic cultures of ICR mouse cerebellum, we studied the effects of TNF-alpha on myelin formation, and its demyelinating effects. Mature, myelinated cultures were resistant to TNF-alpha, even at the highest concentration examined, 1x4^4U/ml. However, when cultures were grown in medium containing TNF-alpha from the time of explantation, myelin formation was significantly affected at a concentration of 1x10^2U/ml. These results suggest that TNF-alpha may be involved in the remyelination block following acute myelin breakdown.The chronic demyelinated plaque of multiple sclerosis (MS) is characterized by a loss of oligodendrocyteastrogliosis, and incomplete or no remyelinatio which probably results in part from the suppressive effects of gliotic astrocytes on myelin formation. We explanted mouse cerebella on astrocyte cultures which had benn maintained for 2 to 12 weeks and assessed the myelination in the cerebellar tissue at 18 days after explantaion. Myelination occurred vigorously in the tissue explanted on 2- to 4-week-old astrocytes, but was poorer in the tissue explanted on astrocytes older than 4 weeks. No myelin sheath was formed on 12-week-old astrocytes, although axons developed equally as well as those in the tissues explanted on 2-week-old astrocytes. As astrocytes were maintained longer, they become fibrous and immunostained more deeply with anti-glial fibrillary acidic protein antibody, being analogous to astrogliosis. These findings imply that astrogliosis in chronic demyelinated lesions of MS may potentially block remyelination.