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Related Experiment Videos

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

H Broholm1, B Andersen, B Wanscher

  • 1Department of Pathology, Glostrup Hospital, Denmark.

Acta Neurologica Scandinavica
|March 16, 2004
PubMed
Summary

Nitric oxide (NO) synthase is highly expressed in multiple sclerosis (MS) brain lesions and normal-appearing white and gray matter. This suggests NO plays a role in MS pathogenesis.

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Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
  • The role of nitric oxide (NO) in MS pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the expression and activity of nitric oxide synthase (NOS) isoforms in MS brain tissue.
  • To determine if NOS expression correlates with lesion activity and normal-appearing white and gray matter.

Main Methods:

  • Post-mortem brain biopsies from four MS patients were obtained using magnetic resonance imaging (MRI) guidance.
  • Immunoreactivity (IR) for inducible, neuronal, and endothelial NOS (iNOS, nNOS, eNOS) isoforms and enzymatic NOS activity were analyzed.
  • Histological examination identified active and inactive lesions.

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Main Results:

  • MRI-guided biopsies revealed more active lesions than macroscopic examination.
  • iNOS was the dominant NOS isoform, primarily expressed by reactive astrocytes in active lesions.
  • NOS-expressing cells were found in plaques and macroscopically normal white and gray matter, including areas appearing normal on MRI.
  • eNOS was highly expressed in intraparenchymal vascular endothelial cells of MS patients, but not in controls.

Conclusions:

  • NO is implicated as a pathogenic factor in MS.
  • NOS is strongly expressed in active MS lesions and also in brain regions that appear normal on MRI, suggesting a role in early disease processes.