Studies of Myelin Breakdown in Vitro

Relationship of iron to oligondendrocytes and myelination

“…Thus, macrophages infiltrating into multiple sclerosis lesions would find a ready supply of iron in oligodendrocytes and would also secrete cytokines and reactive metabolites of oxygen, both of which would be harmful to oligodendrocytes (Guilian, 1987;Takemura and Werb, 1984). These ideas are consistent with the findings that activated macrophages are associated with multiple sclerosis lesions and may stimulate myelin breakdown (Fisher et al, 1988;Johnson et al, 1989). Specific cytokines such as interleukin-2, interleukin-6, and TNF, which are secreted by microglia and macrophages, decrease secretion of Tf from Sertoli cells (Boockfor and Schwarz, 1991) and could have the same effect on oligodendrocytes, limiting their ability to acquire sufficient iron for remyelination.…”

“…Circumstantial evidence that oxidative stress could be related to demyelination is provided by observations that macrophages from patients with multiple sclerosis have increased production of superoxide radicals and hydrogen peroxide (Fisher et al, 1988). The release of superoxide radicals from macrophages is part of the microbicidal and tumoricidal activity of these cells (Takemura and Werb, 1984) but may exacerbate myelin breakdown in the multiple sclerosis lesion site (Fisher et al, 1988;Johnson et al, 1989). A role for free radical-induced lipid damage and subsequent demyelination may extend beyond multiple sclerosis, since siderotic microglia have been reported in white matter of patients with the acquired immunodeficiency syndrome (Gelman et al, 1992).…”

Oligodendroglial cell death induced by oxygen radicals and its protection by catalase

“…Recent studies have reported that macrophages obtained from patients with multiple sclerosis produced increased amounts of hydrogen peroxide and superoxide radicals as compared with normal controls and that these activated macrophages may have a role in the pathogenesis of OL injury and demyelination in multiple sclerosis (Fischer et al, 1988;Johnson et al, 1989).…”

“…In conclusion, we demonstrated that the oxygen radicals generated by the enzymatic system induced lethal toxic effects on bovine OL that have an important function in producing and maintaining CNS myelin. Recent studies have reported that macrophages obtained from patients with multiple sclerosis produced increased amounts of hydrogen peroxide and superoxide radicals as compared with normal controls and that these activated macrophages may have a role in the pathogenesis of OL injury and demyelination in multiple sclerosis (Fischer et al, 1988;Johnson et al, 1989).…”

“…There is currently much interest in the role of oxygen radicals, generated by activated macrophages, in the myelin breakdown in multiple sclerosis (Johnson et al, 1989). It is generally thought that autoimmune processes are involved in multiple sclerosis (Ellison, 1984;Waksman, 1989) and monocytes/macrophages act as mediators of myelin destruction.…”