Tumor necrosis factor-alpha (TNF-alpha) retards the rate of terminal maturation of oligodendrocytes in vitro. The following respective compounds were used along with TNF-alpha in order to try and restore the normal rate of maturation: (1) the antioxidant, coenzyme Q(10) (CoQ(10)); (2) the antioxidant, N-acetyl cysteine (NAC); (3) creatine, which helps to preserve cellular energy; and (4) S-adenosyl methionine (SAM), which contributes to the biosynthesis of lipids and proteins. Of these compounds, only CoQ(10) or NAC was able to restore the numbers of mature myelin basic protein-positive cells and the ability of the oligodendrocytes to form membrane sheets. If TNF-alpha treatment causes oxidative damage by compromising oxidative metabolism in oligodendrocytes, increasing products of lipid peroxidation and/or generating radical oxygen species that can interfere with maturation signals, CoQ10 and NAC may protect oligodendrocytes by reversing one or more of those destructive processes during terminal maturation. (C) 2002 Elsevier Science Inc. All rights reserved.