Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible.
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.
Redford
E J
EJ
Department of Neurology, UMDS-Guy's Campus, London, UK.
Kapoor
R
R
Smith
K J
KJ
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D003711:Demyelinating Diseases / Q000503:physiopathology; D004996:Ethidium / Q000008:administration & dosage / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology; D008845:Microinjections; D009169:Mycobacterium tuberculosis; D009186:Myelin Sheath / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects*; D009444:Neuritis, Autoimmune, Experimental / Q000503:physiopathology; D009569:Nitric Oxide / Q000494:pharmacology*; D009589:Nitrogen Oxides; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D010543:Peroneal Nerve / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D012584:Sciatic Nerve / Q000502:physiology; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013979:Tibial Nerve / Q000502:physiology
D008244:Lysophosphatidylcholines; D009589:Nitrogen Oxides; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D004996:Ethidium; D010396:Penicillamine