Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase

Weiguo Zhao, Ronald Tilton, John A. Corbett, Michael L. McDaniel, Thomas P. Misko, Joseph R. Williamson, Anne H. Cross, William F. Hickey

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Abstract

This study assessed the role of de novo nitric oxide (NO) production in the pathogenesis of experimental allergic encephalomyelitis (EAE) by using aminoguanidine (AG), an inhibitor of nitric oxide synthase (NOS), which preferentially inhibits the cytokine- and endotoxin-inducible isoform of NOS versus the constitutive isoforms consisting of endothelial and neuronal NOS. The maximum clinical severity of EAE and the duration of illness were significantly reduced or totally inhibited by twice daily subcutaneous injection of 100 mg/kg body weight AG. Histochemical staining for NADPH diaphorase, which detects enzymatic activity of NOS, revealed positive reactivity in untreated EAE rats both in parenchymal blood vessel walls and in anterior horn cell neurons, while normal rats and rats with EAE treated with AG showed predominantly the neuronal positivity. Moreover, this NADPH staining pattern was further supported by the immunohistochemical findings that endothelial NOS (eNOS) expression was increased in blood vessels in the inflamed lesions of untreated EAE rats and that inducible NOS (iNOS) was detected in some infiltrating inflammatory cells, while treatment with AG could significantly reduce both iNOS and eNOS production. These results suggest that: (i) both iNOS and eNOS are upregulated in inflamed areas of the rat central nervous system in EAE; (ii) increased NO production plays a role in the development of clinical signs in EAE; and (iii) selective inhibitors of iNOS and/or eNOS may have therapeutic potential for the treatment of certain autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)123-133
Number of pages11
JournalJournal of Neuroimmunology
Volume64
Issue number2
DOIs
StatePublished - Feb 1996
Externally publishedYes

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Keywords

  • Aminoguanidine
  • Experimental allergic encephalomyelitis
  • Multiple sclerosis
  • NADPH diaphorase
  • Nitric oxide

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Zhao, W., Tilton, R., Corbett, J. A., McDaniel, M. L., Misko, T. P., Williamson, J. R., Cross, A. H., & Hickey, W. F. (1996). Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase. Journal of Neuroimmunology, 64(2), 123-133. https://doi.org/10.1016/0165-5728(95)00158-1