A brand new paper, available in toto from BRAIN, A Journal of Neurology.
http://brain.oxfordjournals.org/content/early/2011/06/07/brain.awr128.full.pdf+html
Check it out, read the charts, look at the illustrations....it is a very thorough study.
You may recognize the name Lassmann from his previous studies on how early lesions in MS look like ischemic/hypoxic injury, and that the immune reaction is secondary. Marie writes about Lassmann (as well as Prineas and Barnett, who are referenced in this paper) in her book. www.ccsvibook.com
This new study looks more closely at oxidative damage by studying autopsy brain material:
This study was performed on paraffin-embedded archival autopsy material from 30 patients with multiple sclerosis, one patient with neuromyelitis optica and 24 controls without neurological disease or brain lesions (Table 1). Controls included 17 normal controls of different age and seven patients, who died under septic conditions.
To date, the mechanisms of tissue injury and neurodegeneration in multiple sclerosis are poorly understood. Demyelination and axonal injury occurs on a background of chronic inflammation in the relapsing as well as in the progressive stage of the disease (Frischer et al., 2009) and close contacts between activated micro- glia or macrophages and degenerating axons, myelin sheaths and oligodendrocytes have been described (Ferguson et al., 1997; Trapp et al., 1998; Kornek et al., 2000). Reactive oxygen species and nitric oxide intermediates are produced by activated macrophages and microglia and are, thus, likely candidates to be involved in tissue injury in multiple sclerosis (Van Hoorsen et al., 2010).
In contrast to these previous studies, we show here that DNA and lipid oxidation is associated with ongoing demyelination and neurodegeneration in active multiple sclerosis lesions. Furthermore, we show for the first time that acute cell injury and cell death of oligodendrocytes, axons and neurons in multiple sclerosis is linked to profound cytoplasmic and nuclear oxidative damage. The reason for the different results between our current and previous studies is not entirely clear. The most likely explanation comes from our observation that oxidized DNA and lipids were mainly present in a small zone of active multiple sclerosis lesions, which represents that previously described as the area of initial demyelination (Marik et al., 2007) or the ‘prephagocytic’ lesion (Barnett and Prineas, 2004; Henderson et al., 2009). Such lesions or lesion areas may not have been included in earlier studies. It has been shown previously that oxidized phospholipids and MDA epitopes are present in apoptotic cells as well as in apoptotic bodies ingested by macrophages (Chang et al., 1999). Apoptotic oligodendrocytes are predominantly seen in multiple sclerosis lesions in areas of initial (prephagocytic) demyelination (Barnett and Prineas, 2004; Marik et al., 2007). Furthermore, apoptotic cell death through oxidative mechanisms may exert proinflammatory and immunogenic actions (Chang et al., 2004), which in part may explain the progressive increase in inflammation with lesion maturation in multiple sclerosis (Marik et al., 2007; Henderson et al., 2009).
In summary, our study provides evidence for an important role of oxidative damage in the pathogenesis of demyelination and neurodegeneration in multiple sclerosis lesions, which may act in addition to, or in cooperation with nitric oxide radicals, as described previously (Bagasra et al., 1995; Zeis et al., 2009). It further shows—for the first time—that the analysis of oxidized lipid epitopes in multiple sclerosis lesions allows identification of acute damage of oligodendrocytes, axons and neurons at different stages of lesion formation. Our data also suggest that oxidative damage is in part related to inflammation, that it affects different cellular components of the CNS, but that myelin, oligodendrocytes, neurons and axons may be more sensitive to oxidative damage than astrocytes.
-If oxidative stress is indeed the initiating event which begins cellular death, formation of the MS lesion and inflammation, and MS damage is not initiated by the immune system....we need to stop using EAE as the model for MS, and marketing drugs which use this model. Oxidative stress is well understood in cardiovascular disease and ischemic injuries. Time to get the right model for MS---
Joan