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 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.
Conti
Giancarlo
G
Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. contigiancarlo@hotmail.com
Rostami
Abdolmohammed
A
Scarpini
Elio
E
Baron
PierLuigi
P
Galimberti
Daniela
D
Bresolin
Nereo
N
Contri
Miranda
M
Palumbo
Carla
C
De Pol
Anto
A
D000818:Animals; D015152:Blotting, Northern; D002463:Cell Membrane Permeability / Q000502:physiology; D003711:Demyelinating Diseases / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004790:Enzyme Induction / Q000502:physiology; D007150:Immunohistochemistry; D009412:Nerve Fibers / Q000201:enzymology / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D017933:Peripheral Nervous System / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000201:enzymology / Q000473:pathology; D014855:Wallerian Degeneration / Q000201:enzymology* / Q000473:pathology
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat