The cerebrospinal fluid from patients with multiple sclerosis promotes neuronal and oligodendrocyte damage by delayed production of nitric oxide in vitro.
Nitric oxide (NO) may be involved in myelin and oligodendrocyte injury associated with multiple sclerosis (MS), a demyelinating disease of unknown etiology. The cerebrospinal fluid (CSF) from MS patients may provide an important signal inducing a pathologic process within the central nervous system (CNS). To investigate this question, CSF-induced NO production by glial cells was studied in 38 patients with multiple sclerosis (MS), 30 patients with other CNS inflammatory diseases (ID) and 20 with tension headache (TH) as control. Neuron damage was estimated by release of lactate dehydrogenase (LDH), whereas oligodendrocyte damage was estimated by a percentage of viable cells in primary oligodendrocyte cultures. Here we show that CSFs from 13/38 (34%) patients with MS stimulate glial cells to produce NO, compared to 2/20 (10%) of patients with ID and 1/30 (3%) with tension headache. The levels of NO production correlated positively with the amounts of LDH released and negatively with percentage of viable oligodendrocytes, suggesting that NO may represent a mechanism for oligodendrocyte losses in affected tissues and play a role in lesion formation in MS and its animal model experimental allergic encephalomyelitis (EAE).
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
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Xiao
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Zhang
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Ma
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D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D002556:Cerebrospinal Fluid Proteins / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D002556:Cerebrospinal Fluid Proteins; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase