Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Multiple Sclerosis (MS) is an immune mediated disease characterized by numerous plaques which contain demyelinated axons, perivascular T-lymphocytes and macrophages (Rodriguez and Scheithauer, 1994; Brosnan and Raine, 1996). The early MS lesion contains inflammatory cytokines and reactive oxygen and nitrogen species that are produced by immune cells as well as reactive astrocytes and microglia (Banati et al, 1993; Vladutiu, 1995; Brosnan et al, 1994). Furthermore, overwhelming evidence suggests that it is this inflammatory environment which may facilitate the development of the demyelinated axons in these plaques (Brosnan and Raine, 1996, Raine, 1997, Zhao and Schwartz, 1998) in that these molecules are directly involved in the loss of oligodendrocyte cell numbers (Mackenzie-Graham et al, 1994) and myelin destruction (Selmaj and Raine, 1988; Bruck et al, 1994).

Release of inflammatory cytokines and reactive species during inflammation is dependent in part upon the presence and activation of macrophages. While the role of macrophages in demyelinating plaques is unknown, research has shown that these cells may contribute to demyelination via the release of 1) certain inflammatory cytokines (Brosnan and Raine, 1996; Ludwin, 1997; Zhao and Schwartz, 1998), 2) complement proteins (DeJong and Smith, 1997) 3) free radicals (Brosnan et al, 1994; Bruck et al, 1994) and 4) by the phagocytosis of myelin fragments (Bruck et al, 1994). However, in certain situations the inflammatory aspects associated with macrophages have been demonstrated to promote recovery from injury and to promote nerve regeneration (Schwartz et al., 1997, Cuzner et al., 1994). Furthermore, addition of macrophages to myelinating aggregate cultures promotes myelination (Loughlin et al., 1994; 1997) while addition of macrophages to lysolecithin-induced demylinated dorsal columns of mice promotes remyelination (Pavelko et al., 1998).

The objectives of this study were two-fold: 1) to delineate the effects of oxidative stress, in the absence of other inflammatory factors, on the maintenance of the myelin sheath, and 2) to determine whether macrophages promoted or diminished the effect of oxidative stress on a myelinating aggregate culture system.

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