Increased expression of PGC-1alpha and downstream mitochondrial antioxidants in active MS lesions. MS lesions are characterized by loss of proteolipid protein (PLP; A). In early active lesions densely packed macrophages containing myelin proteins are present (B, inset), late active lesions typically contain MHCII positive leukocytes throughout the lesion area (C). Chronic active MS lesions are characterized by a rim of activated microglia/macrophages at the border of the lesion which are absent in the lesion center (D). Low PGC-1α, Prx3 and Trx2 immunostaining was observed in the NAWM (E-G, insets). Early active lesions showed enhanced PGC-1α, Prx3 and Trx2 immunoreactivity in astrocytes (arrow) and oligodendrocytes (arrowhead) (H-J, insets). In late active lesion expression is predominantly localized to astrocytes (arrow) (K-M, insets), which was largely lost in the inactive center of chronic active lesions (N-P).