PDF(Pubmed)
Abstract：
Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species.
摘要：
急性视神经炎的视力丧失通常归因于炎性脱髓鞘所致的轴突传导阻滞，但机制尚不清楚。最近的研究强调了组织缺氧是多发性硬化症（MS）和实验性自身免疫性脑脊髓炎（EAE）的神经功能缺损和组织损伤的重要原因，在这里，我们检查了在DarkAgouti大鼠诱发的实验性视神经炎中视神经是否缺氧。在疾病表达的第一个和第二个高峰，发炎的视神经明显标记为组织缺氧(即，缺氧诱导因子-1α（HIF1α）阳性，静脉注射吡莫硝唑）。急性发炎的神经也被显著标记为氧化和硝化应激和损伤的先天标志物，包括超氧化物,一氧化氮和3-硝基酪氨酸.毛细血管的密度和直径也增加。我们得出结论，在急性视神经炎中，视神经缺氧，受到氧化和硝化的压力和损伤。组织缺氧可导致线粒体衰竭，从而解释由于轴突传导阻滞导致的视力丧失。组织缺氧还可以诱导破坏性的氧化和硝化环境。研究结果表明，在急性视神经炎中预防组织缺氧的治疗可能有助于恢复视力并防止损害活性氧和氮。
