NITRIC-OXIDE DONORS REVERSIBLY BLOCK AXONAL CONDUCTION - DEMYELINATEDAXONS ARE ESPECIALLY SUSCEPTIBLE

Diseases such as multiple sclerosis and Guillain-Barre syndrome are ch aracterized not only by widespread loss of myelin from nerve fibres, b ut also by widespread inflammation in the central and peripheral nervo us systems, respectively. While the demyelination alone is sufficient to block conduction and thereby cause symptoms, there is increasing ev idence that the inflammation may also contribute significantly to the conduction block, although the mechanisms are not understood. Nitric o xide is an important inflammatory mediator which is elevated within th e central nervous system in multiple sclerosis and which can be experi mentally applied to tissues using nitric oxide donors. We report that such compounds cause reversible conduction block in both normal and de myelinated axons of the central and peripheral nervous systems. Notabl y, conduction in demyelinated and early remyelinated axons is particul arly sensitive to block by nitric oxide, so that at lower concentratio ns, including those expected at sites of inflammation, demyelinated ax ons are selectively affected We therefore propose that inflammation ma y directly cause symptoms via nitric oxide release, and that the inhib ition of such release may open a new therapeutic avenue for demyelinat ing disease.