Myelin phagocytosis and remyelination of macrophage-enriched central nervous system aggregate cultures

An increased level of myelin basic protein (MBP) degradation peptide 80-89, representative of myelin breakdown, is detected in myelinating foetal rat brain aggregate cultures supplemented with peritoneal macrophages at a time coinciding with the onset of myelination. During the period of myelination , the proportion of activated macrophages/microglia in the aggregates decre ases, accompanied by a reduction in the content of MBP degradation products . During the recovery period following a demyelinating episode, the rate of MBP synthesis in antibody-treated standard aggregates was greater than in their medium controls. However, the rate of MBP accumulation was not as eff icient in macrophage-enriched aggregates and was associated with persistent ly raised MBP peptide levels. Thus, as occurs in multiple sclerosis lesions , attempts at remyelination appear to be counterbalanced by macrophage-medi ated demyelination, with the continued presence of degraded myelin renderin g a local environment that is not fully conducive to remyelination. (C) 200 1 Wiley-Liss, Inc.