Macrophages: their myelinotrophic or neurotoxic actions depend upon tissueoxidative stress

There are still questions regarding whether macrophages found in MS lesions ore agents of recovery or of destruction. To address this, we examined in aggregate cultures prepared from dissociated embryonic spinal cord tissue, with or without addition of exogenous macrophages, the effect of menadione- induced oxidative stress. Similar to findings of other laboratories, we obs erved that in the absence of oxidative stress macrophage enrichment Promote d myelinogenesis. In macrophage-poor cultures, menadione at 5 mu M had very little effect upon the status of the aggregate cultures; however, increasi ng this to 10 and 20 mu M did result in some damage to axons and myelin. By contrast in macrophage enriched cultures, menadione at a concentration as little as 5 mu M caused the complete destruction of the aggregates We sugge st that in neural tissues that have sufficiently high macrophage numbers, o xidative stress results in a positive inflammatory feedback loop that resul ts in massive tissue destruction. We further suggest that what we see in ma crophage-enriched aggregates subjected to oxidative stress may represent wh at happens in the Marburg-type of MS lesion.