Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible

被引:254
作者
Redford, EJ
Kapoor, R
Smith, KJ
机构
[1] UMDS, Sch Med, Dept Neurol, London SE1 9RT, England
[2] UCL Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England
关键词
nitric oxide donors; conduction block; demyelination; inflammation;
D O I
10.1093/brain/120.12.2149
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Diseases such as multiple sclerosis and Guillain-Barre 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.
引用
收藏
页码:2149 / 2157
页数:9
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