Newly lesioned tissue in multiple sclerosis--a role for oxidative damage?

The causes of lesion formation in multiple sclerosis remain uncertain. While an autoimmune pathogenesis is favoured by many (Weiner, 2004; Frohman et al. , 2006), innate immune mechanisms have also been proposed (Barnett and Prineas, 2004; Marik et al. , 2007), in addition to roles for bacteria and viruses (Gay, 2007; Salvetti et al. , 2009). This issue of Brain includes two papers on multiple sclerosis lesions, which may illuminate mechanisms involved in their formation (Haider et al ., 2011) and repair (Zambonin et al ., 2011).Hans Lassmann and colleagues have explored their bank of multiple sclerosis tissue seeking information on oxidative damage (Haider et al. , 2011). The authors uncover abundant evidence of oxidized lipids and DNA in active multiple sclerosis lesions, significantly adding to our understanding from earlier observations (Graumann et al. , 2003; Gray et al. , 2008 b ; Zeis et al. , 2009; van Horssen et al. , 2011). Lipid peroxides and oxidized nuclear DNA were mainly present in oligodendrocytes, often associated with evidence of apoptosis: a small number of reactive astrocytes were also affected. Oxidized phospholipids were also ‘massively’ accumulated in some axonal spheroids and neurons, many of which appeared to be degenerating.Oxidative damage ensues when pro-oxidant factors (see below) overwhelm the inherent anti-oxidant defences of cells and tissues, resulting in oxidative stress and oxidative modification of biological molecules such as enzymes, lipids and DNA, thereby preventing normal cellular function and increasing the likelihood of cell death. The profound oxidative damage found in oligodendrocytes and axons is therefore important because it will undoubtedly contribute to the ongoing demyelination and axonal injury and degeneration, and perhaps may even be causative.The existence of oxidative damage within active multiple sclerosis lesions is not in itself surprising, because the …