Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Recent in vitro experiments suggest that damage to oligodendrocytes and myelin sheaths in inflammatory demyelinating diseases may in part be the result of elevated levels of free radicals. The objective of this study was to determine the effect of menadione generated superoxide on cell viability and myelin morphology in the presence or absence of suspected free radical generating cells, macrophages. Spinal cord aggregate cultures were grown in the presence or absence of enriched macrophages until myelinated, then treated with 5, 10, or 20 µM menadione and sampled at 24, 48, and 96 hours. Cell necrosis, neuropil cavitation and damage to myelin profiles were observed 24 hours after menadione exposure. Maximum damage was seen 48 hours following exposure but did not progress beyond this time point. Aggregates to which macrophages had been added, that were exposed to menadione, exhibited a dramatic loss of neuropil, widespread non-specific cell necrosis and extensive demyelination of myelinated axons throughout the entire aggregate, even at the lowest concentrations. By 48 hours, aggregates were almost devoid of cellular detail. By 96 hours, all cellular structure was obliterated. The substantial cell damage increases in these cultures may be explained by the initiation of free radical induced feedback, resulting in continued activation of macrophages and continual release of additional cytotoxic factors into the area. Taken together, the results obtained support a role for free radicals in the damage associated with inflammatory demyelinating diseases and suggests that such damaging effects are exacerbated by the presence of macrophages.

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Poster Number PAdevon0759
Keywords: myelin, free readical, inflammation, cns, damage