NOS in MS

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Bottom line: More NOS=more NO= more peroxynitrite=more neuronal

damage

Authors

Broholm H. Andersen B. Wanscher B. Frederiksen JL. Rubin I.

Pakkenberg B. Larsson HB. Lauritzen M.

Institution

Department of Pathology, Glostrup Hospital, Denmark.

Title

Nitric oxide synthase expression and enzymatic activity in multiple

sclerosis.

Source

Acta Neurologica Scandinavica. 109(4):261-9, 2004 Apr.

Abstract

We used post-mortem magnetic resonance imaging (MRI) guidance to

obtain paired biopsies from the brains of four patients with

clinical definite multiple sclerosis (MS). Samples were analyzed for

the immunoreactivity (IR) of the three nitric oxide (NO) synthase

isoforms [inducible, neuronal and endothelial nitric oxide synthase

(NOS)], and enzymatic NO synthase activity. MRI guided biopsies

documented more active plaques than macroscopic examination, and

histological examination revealed further lesions. Inducible NOS

(iNOS) was the dominant IR isoform, while reactive astrocytes were

the dominant iNOS expressing cells in active lesions. NOS IR

expressing cells were widely distributed in plaques, in white and

gray matter that appeared normal macroscopically, and on MR.

Endothelial NOS (eNOS) was highly expressed in intraparenchymal

vascular endothelial cells of MS patients. A control group matched

for age and sex showed no such changes. Our data support the

hypothesis that NO is a pathogenic factor in MS, and that NOS IR is

strongly expressed in brain regions appearing normal by MRI.