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Related Experiment Videos

Peroxynitrite formation within the central nervous system in active multiple sclerosis

A H Cross1, P T Manning, R M Keeling

  • 1Department of Neurology and Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA. crossa@neuro.wustl.edu

Journal of Neuroimmunology
|August 4, 1998
PubMed
Summary

Peroxynitrite, a damaging oxidant formed during inflammation, was detected in multiple sclerosis (MS) central nervous system (CNS) tissues. Elevated nitrate levels during MS relapses suggest peroxynitrite contributes to MS pathogenesis.

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Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • Peroxynitrite is a potent oxidant generated from nitric oxide (NO) and superoxide during inflammation.
  • Nitrotyrosine (NT) is a biomarker for peroxynitrite-induced cellular and tissue damage.
  • Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS).

Purpose of the Study:

  • To investigate the presence and role of peroxynitrite in the pathogenesis of Multiple Sclerosis (MS).
  • To assess nitrotyrosine (NT) as a marker of peroxynitrite-mediated damage in MS CNS tissues.
  • To measure levels of NO oxidation products (nitrite and nitrate) in cerebrospinal fluid (CSF) of MS patients.

Main Methods:

  • Immunohistochemical detection of NT in autopsied CNS tissues from MS patients and controls.

Related Experiment Videos

  • Measurement of nitrite and nitrate concentrations in CSF samples from MS patients and controls using established biochemical assays.

    • Main Results:

    • NT was detected in CNS tissues of six out of nine MS patients, predominantly in inflamed areas.
    • Significantly elevated levels of nitrate were observed in the CSF of MS patients during clinical relapses compared to controls.
    • Nitrite levels did not show significant differences between MS patients and controls.

    Conclusions:

    • Peroxynitrite formation is a significant consequence of nitric oxide production in the MS-affected CNS.
    • The presence of NT and elevated nitrate levels implicate peroxynitrite as a key oxidant contributing to MS pathogenesis.
    • Targeting peroxynitrite-mediated damage may offer a therapeutic strategy for MS.