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Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

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Broholm H, Andersen B, Wanscher B, Frederiksen JL, Rubin I, Pakkenberg B, Larsson HBW, Lauritzen M. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

Acta Neurol Scand 2004: DOI: 10.1111/j.1600-0404.2004.00207.x © Blackwell Munksgaard 2004.

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.

Keywords: NOS enzymatic activity; NOS immunohistochemistry; cytotoxicity; magnetic resonance imaging; multiple sclerosis; nitric oxide synthase; oligodendrocytes

Document Type: Research Article


Affiliations: 1: Pathology 2: Clinical Neurophysiology 3: Neurology, Glostrup Hospital, Denmark 4: Department of Medical Biochemistry and Genetics, University of Copenhagen, Denmark 5: Research Laboratory for Stereology and Neuroscience, Bispebjerg Hospital 6: Danish MRI Research Centre, Hvidovre Hospital, Hvidovre, Denmark

Publication date: April 1, 2004


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