Brain, Vol 120, Issue 12 2149-2157, Copyright © 1997 by Oxford University Press
EJ Redford, R Kapoor and KJ Smith
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.
ARTICLES
Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible
Department of Neurology, UMDS-Guy's Campus, London, UK.
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