Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system

The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that dur...

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Veröffentlicht in:Experimental neurology 2004-06, Vol.187 (2), p.350-358
Hauptverfasser: Conti, Giancarlo, Rostami, Abdolmohammed, Scarpini, Elio, Baron, PierLuigi, Galimberti, Daniela, Bresolin, Nereo, Contri, Miranda, Palumbo, Carla, De Pol, Anto
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container_issue 2
container_start_page 350
container_title Experimental neurology
container_volume 187
creator Conti, Giancarlo
Rostami, Abdolmohammed
Scarpini, Elio
Baron, PierLuigi
Galimberti, Daniela
Bresolin, Nereo
Contri, Miranda
Palumbo, Carla
De Pol, Anto
description The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death.
doi_str_mv 10.1016/j.expneurol.2004.01.026
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NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). 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Prion diseases ; Demyelinating Diseases - enzymology ; Demyelinating Diseases - immunology ; Demyelinating Diseases - pathology ; Demyelination ; Disease Models, Animal ; Disease Progression ; Enzyme Induction - physiology ; Immunohistochemistry ; Injuries of the nervous system and the skull. Diseases due to physical agents ; iNOS ; Medical sciences ; Necrosis ; Nerve Fibers - enzymology ; Nerve Fibers - pathology ; Neuritis, Autoimmune, Experimental - enzymology ; Neuritis, Autoimmune, Experimental - immunology ; Neuritis, Autoimmune, Experimental - pathology ; Neurology ; Nitric Oxide Synthase - genetics ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Peripheral nerve ; Peripheral Nervous System - enzymology ; Peripheral Nervous System - pathology ; Rats ; Rats, Inbred Lew ; Sciatic Nerve - enzymology ; Sciatic Nerve - pathology ; Traumas. 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NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Axonal degeneration</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Cell Membrane Permeability - physiology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Demyelinating Diseases - enzymology</subject><subject>Demyelinating Diseases - immunology</subject><subject>Demyelinating Diseases - pathology</subject><subject>Demyelination</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Enzyme Induction - physiology</subject><subject>Immunohistochemistry</subject><subject>Injuries of the nervous system and the skull. 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Leukodystrophies. Prion diseases</topic><topic>Demyelinating Diseases - enzymology</topic><topic>Demyelinating Diseases - immunology</topic><topic>Demyelinating Diseases - pathology</topic><topic>Demyelination</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Enzyme Induction - physiology</topic><topic>Immunohistochemistry</topic><topic>Injuries of the nervous system and the skull. Diseases due to physical agents</topic><topic>iNOS</topic><topic>Medical sciences</topic><topic>Necrosis</topic><topic>Nerve Fibers - enzymology</topic><topic>Nerve Fibers - pathology</topic><topic>Neuritis, Autoimmune, Experimental - enzymology</topic><topic>Neuritis, Autoimmune, Experimental - immunology</topic><topic>Neuritis, Autoimmune, Experimental - pathology</topic><topic>Neurology</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Peripheral nerve</topic><topic>Peripheral Nervous System - enzymology</topic><topic>Peripheral Nervous System - pathology</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Sciatic Nerve - enzymology</topic><topic>Sciatic Nerve - pathology</topic><topic>Traumas. Diseases due to physical agents</topic><topic>Wallerian Degeneration - enzymology</topic><topic>Wallerian Degeneration - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Conti, Giancarlo</creatorcontrib><creatorcontrib>Rostami, Abdolmohammed</creatorcontrib><creatorcontrib>Scarpini, Elio</creatorcontrib><creatorcontrib>Baron, PierLuigi</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Bresolin, Nereo</creatorcontrib><creatorcontrib>Contri, Miranda</creatorcontrib><creatorcontrib>Palumbo, Carla</creatorcontrib><creatorcontrib>De Pol, Anto</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Conti, Giancarlo</au><au>Rostami, Abdolmohammed</au><au>Scarpini, Elio</au><au>Baron, PierLuigi</au><au>Galimberti, Daniela</au><au>Bresolin, Nereo</au><au>Contri, Miranda</au><au>Palumbo, Carla</au><au>De Pol, Anto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>187</volume><issue>2</issue><spage>350</spage><epage>358</epage><pages>350-358</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell–axon relationship causing axonal damage and regulating endoneurial cell life and death.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>15144861</pmid><doi>10.1016/j.expneurol.2004.01.026</doi><tpages>9</tpages></addata></record>
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subjects Animals
Apoptosis
Axonal degeneration
Biological and medical sciences
Blotting, Northern
Cell Membrane Permeability - physiology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Demyelinating Diseases - enzymology
Demyelinating Diseases - immunology
Demyelinating Diseases - pathology
Demyelination
Disease Models, Animal
Disease Progression
Enzyme Induction - physiology
Immunohistochemistry
Injuries of the nervous system and the skull. Diseases due to physical agents
iNOS
Medical sciences
Necrosis
Nerve Fibers - enzymology
Nerve Fibers - pathology
Neuritis, Autoimmune, Experimental - enzymology
Neuritis, Autoimmune, Experimental - immunology
Neuritis, Autoimmune, Experimental - pathology
Neurology
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Peripheral nerve
Peripheral Nervous System - enzymology
Peripheral Nervous System - pathology
Rats
Rats, Inbred Lew
Sciatic Nerve - enzymology
Sciatic Nerve - pathology
Traumas. Diseases due to physical agents
Wallerian Degeneration - enzymology
Wallerian Degeneration - pathology
title Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system
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