title: Role of nitric oxide as mediator of nerve injury in inflammatory neuropathies.
abstract: Different lines of evidence suggest that nitric oxide (NO) plays a key role in the pathogenesis of inflammatory neuropathies; however, it is still unclear which structures in the peripheral nerve are the primary targets of NO-mediated nerve injury. To address this issue, we determined the expression of NO metabolites in sural nerve biopsies and in cerebrospinal fluid from patients with inflammatory neuropathies and studied the pathologic effects of NO in an in vitro model of myelinated Schwann cell-neuron cocultures. In cerebrospinal fluid samples, nitrite levels remained unaltered; however, nitrotyrosine, a marker for peroxynitrite formation, could be identified in nerve biopsies from patients with inflammatory neuropathies. In an in vitro model of Schwann cell neuron cocultures, high concentrations of NO induced robust demyelination, which was the result of NO-mediated axonal injury, whereas Schwann cell viability remained unaffected. These findings suggest that in contrast to Schwann cells, sensory neurons are the primary target of NO-mediated cytotoxicity and the loss of myelin is the result of selective damage to axons rather than a direct harmful effect to Schwann cells. Our findings imply that NO contributes to the pathologic changes seen in the inflamed peripheral nervous system, which is characterized by the features of axonal injury and subsequent myelin degradation, previously described as Wallerian-like degeneration.
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. helmar.lehmann@uni-duesseldorf.de
authors.forename: Helmar C
authors.initials: HC
authors.lastname: Lehmann
authors.forename: Angelika
authors.initials: A
authors.lastname: Köhne
authors.forename: Gerd
authors.initials: G
authors.lastname: Meyer zu Hörste
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.forename: Olivia
authors.initials: O
authors.lastname: Kiehl
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Stefan
authors.initials: S
authors.lastname: Kastenbauer
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D016166:Free Radical Scavengers / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000633:toxicity; D009603:Nitroso Compounds / Q000633:toxicity; D011129:Polyradiculoneuropathy / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D012583:Schwann Cells / Q000737:chemistry; D013497:Sural Nerve / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid
chemical_list: D017077:Culture Media, Conditioned; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007093:Imidazoles; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine