Centre for Brain Research, Medical University of Vienna, Wien, Austria.
Nat Rev Neurol. 2012 Nov 5;8(11):647-56. doi: 10.1038/nrneurol.2012.168. Epub 2012 Sep 25.
Major progress has been made during the past three decades in understanding the inflammatory process and pathogenetic mechanisms in multiple sclerosis (MS). Consequently, effective anti-inflammatory and immunomodulatory treatments are now available for patients in the relapsing-remitting stage of the disease. This Review summarizes studies on the pathology of progressive MS and discusses new data on the mechanisms underlying its pathogenesis. In progressive MS, as in relapsing-remitting MS, active tissue injury is associated with inflammation, but the inflammatory response in the progressive phase occurs at least partly behind the blood-brain barrier, which makes it more difficult to treat. The other mechanisms that drive disease in patients with primary or secondary progressive MS are currently unresolved, although oxidative stress resulting in mitochondrial injury might participate in the induction of demyelination and neurodegeneration in both the relapsing-remitting and progressive stages of MS. Oxidative stress seems to be mainly driven by inflammation and oxidative burst in microglia; however, its effects might be amplified in patients with progressive MS by age-dependent iron accumulation in the brain and by mitochondrial gene deletions, triggered by the chronic inflammatory process.
过去三十年，人们在理解多发性硬化症（MS）的炎症过程和发病机制方面取得了重大进展。因此，目前针对疾病缓解-复发阶段的患者，已有有效的抗炎和免疫调节治疗方法。本综述总结了关于进展性 MS 病理学的研究，并讨论了其发病机制的新数据。在进展性 MS 中，与复发缓解性 MS 一样，活跃的组织损伤与炎症有关，但在进展阶段的炎症反应至少部分发生在血脑屏障之后，这使得治疗更加困难。目前，在原发性或继发性进展性 MS 患者中驱动疾病的其他机制尚不清楚，尽管导致线粒体损伤的氧化应激可能参与了复发缓解期和进展期 MS 中的脱髓鞘和神经退行性变。氧化应激似乎主要由小胶质细胞中的炎症和氧化爆发驱动；然而，在进展性 MS 患者中，由于大脑中与年龄相关的铁积累以及由慢性炎症过程引发的线粒体基因缺失，其影响可能会被放大。
