Redford E J, Kapoor R, Smith K J
Department of Neurology, UMDS-Guy's Campus, London, UK.
Brain. 1997 Dec;120 ( Pt 12):2149-57. doi: 10.1093/brain/120.12.2149.
Diseases such as multiple sclerosis and Guillain-Barré syndrome are characterized not only by widespread loss of myelin from nerve fibres, but also by widespread inflammation in the central and peripheral nervous systems, respectively. While the demyelination alone is sufficient to block conduction and thereby cause symptoms, there is increasing evidence that the inflammation may also contribute significantly to the conduction block, although the mechanisms are not understood. Nitric oxide is an important inflammatory mediator which is elevated within the central nervous system in multiple sclerosis and which can be experimentally applied to tissues using nitric oxide donors. We report that such compounds cause reversible conduction block in both normal and demyelinated axons of the central and peripheral nervous systems. Notably, conduction in demyelinated and early remyelinated axons is particularly sensitive to block by nitric oxide, so that at lower concentrations, including those expected at sites of inflammation, demyelinated axons are selectively affected. We therefore propose that inflammation may directly cause symptoms via nitric oxide release, and that the inhibition of such release may open a new therapeutic avenue for demyelinating disease.
诸如多发性硬化症和格林-巴利综合征等疾病的特征不仅在于神经纤维广泛脱髓鞘，还分别在于中枢和周围神经系统的广泛炎症。虽然仅脱髓鞘就足以阻断传导并由此引发症状，但越来越多的证据表明，炎症也可能对传导阻滞有显著影响，尽管其机制尚不清楚。一氧化氮是一种重要的炎症介质，在多发性硬化症的中枢神经系统中含量升高，并且可以使用一氧化氮供体将其实验性地应用于组织。我们报告称，此类化合物会在中枢和周围神经系统的正常和脱髓鞘轴突中引起可逆性传导阻滞。值得注意的是，脱髓鞘和早期再髓鞘化轴突的传导对一氧化氮阻滞特别敏感，因此在较低浓度下，包括炎症部位预期的浓度，脱髓鞘轴突会受到选择性影响。因此，我们提出炎症可能通过一氧化氮释放直接导致症状，并且抑制这种释放可能为脱髓鞘疾病开辟一条新的治疗途径。
