Free radicals are believed to play a role in the pathogenesis of MS. Persons with MS have elevated concentrations of markers of nitric oxide (NO) production, including nitrate and nitrite, in their cerebrospinal fluid (CSF), blood, and urine. Research suggests that NO has a role in the axonal degeneration and impairment of axonal conduction, disruption of the blood-brain barrier, and oligodendrocyte injury and demyelination in MS.12 NO is also found in increased concentrations in inflammatory MS lesions, possibly as the result of increased expression of inducible nitric oxide synthase (iNOS) by astrocytes and macrophages. Astrocytes, macrophages, and oligodendrocytes in these lesions have also shown elevated levels of nitrotyrosine, indicating the presence of peroxynitrite, a highly reactive metabolite of NO, that may be the primary source of injury of oligodendrocytes in MS patients.13 A study of CSF levels of nitrate and nitrite in MS patients over a period of three years found increased CSF levels of nitrate and nitrite in mildly disabled individuals, which correlated with the volume of lesions found on magnetic resonance imaging (MRI). Greater than normal levels of nitrate and nitrite in the CSF at the time of baseline examination of MS patients also correlated with clinical progression of the disease and with MRI results.14
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