Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

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.

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.