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Immunization with A91 peptide or copolymer‐1 reduces the production of nitric oxide and inducible nitric oxide synthase gene expression after spinal cord injury
Author(s) -
García Elisa,
SilvaGarcía Raúl,
Mestre Humberto,
Flores Nayeli,
Martiñón Susana,
CalderónAranda Emma S.,
Ibarra Antonio
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22771
Subject(s) - neuroprotection , nitric oxide , nitric oxide synthase , lipid peroxidation , pharmacology , immune system , spinal cord injury , spinal cord , microbiology and biotechnology , immunology , chemistry , biology , biochemistry , neuroscience , antioxidant , endocrinology
Abstract Immunization with neurally derived peptides (INDP) boosts the action of an autoreactive immune response that has been shown to induce neuroprotection in several neurodegenerative diseases, especially after spinal cord (SC) injury. This strategy provides an environment that promotes neuronal survival and tissue preservation. The mechanisms by which this autoreactive response exerts its protective effects is not totally understood at the moment. A recent study showed that INDP reduces lipid peroxidation. Lipid peroxidation is a neurodegenerative phenomenon caused by the increased production of reactive nitrogen species such as nitric oxide (NO). It is possible that INDP could be interfering with NO production. To test this hypothesis, we examined the effect of INDP on the amount of NO produced by glial cells when cocultured with autoreactive T cells. We also evaluated the amount of NO and the expression of the inducible form of nitric oxide synthase (iNOS) at the injury site of SC‐injured animals. The neural‐derived peptides A91 and Cop‐1 were used to immunize mice and rats with SC injury. In vitro studies showed that INDP significantly reduces the production of NO by glial cells. This observation was substantiated by in vivo experiments demonstrating that INDP decreases the amount of NO and iNOS gene expression at the site of injury. The present study provides substantial evidence on the inhibitory effect of INDP on NO production, helpingour understanding of the mechanisms through which protective autoimmunity promotes neuroprotection. © 2011 Wiley Periodicals, Inc.