Distribution of Inducible Nitric Oxide Synthase and Tumor Necrosis Factor-α in the Peripheral Nervous System of Lewis Rats during Ascending Paresis and Spontaneous Recovery from Experimental Autoimmune Neuritis
- 1 October 2009
- journal article
- research article
- Published by S. Karger AG in Neuroimmunomodulation
- Vol. 17 (1), 56-66
- https://doi.org/10.1159/000243086
Abstract
Background: Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) are pleiotropic molecules with widespread action in autoimmune diseases. Objective: This study characterizes the distribution of iNOS and TNF-α in the spinal nerve roots, dorsal root ganglia and sciatic nerve of Lewis rats during experimental autoimmune neuritis (EAN). Methods: Macrophages and neutrophils were identified by immunofluorescence as cellular sources of iNOS and TNF-α at various stages of EAN induced by synthetic peptide 26. Results: As the disease progressed, iNOS- and TNF-α-bearing cells gradually infiltrated the cauda equina, dorsal root ganglia, Th12–L3 spinal roots, and the sciatic nerve. A severer EAN profile developed when more iNOS- and TNF-α-bearing cells were present, and the recovery from EAN was related to the disappearance of these cells and the regeneration of nerve fibers. Conclusions: This is the first report to show iNOS- and TNF-α-immunoreactive cells in dorsal root ganglia during EAN, suggesting an underlying pathology for the neuropathic pain behavior in EAN. Our results suggest that the cells bearing iNOS and TNF-α in the different parts of the peripheral nervous system are involved in the development of the clinical signs observed at each stage of EAN.Keywords
This publication has 12 references indexed in Scilit:
- Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocyclineJournal of Cellular and Molecular Medicine, 2009
- IL-12– and IL-23–modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibitionThe Journal of Experimental Medicine, 2008
- Spinal changes associated with mechanical hypersensitivity in a model of Guillain–Barré syndromeNeuroscience Letters, 2008
- Mechanical allodynia and spinal up-regulation of P2X4 receptor in experimental autoimmune neuritis ratsNeuroscience, 2008
- Pain hypersensitivity in rats with experimental autoimmune neuritis, an animal model of human inflammatory demyelinating neuropathyBrain, Behavior, and Immunity, 2007
- Pharmacological strategies for the regulation of inducible nitric oxide synthase: Neurodegenerative versus neuroprotective mechanismsNeurochemistry International, 2006
- TNFα-induced MMP-9 promotes macrophage recruitment into injured peripheral nerveMolecular and Cellular Neuroscience, 2005
- Satellite glial cells in sensory ganglia: from form to functionBrain Research Reviews, 2005
- Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous systemExperimental Neurology, 2004
- Blockers of sodium and calcium entry protect axons from nitric oxide‐mediated degenerationAnnals of Neurology, 2002