Lam, Magdalena and Maghzal, Ghassan J and Khademi, Mohsen and Piehl, Fredik and Ratzer, Rikke and Romme Christensen, Jeppe and Sellebjerg, Finn Thorup and Olsson, Tomas and Stocker, Roland (2016) Absence of systemic oxidative stress and increased CSF prostaglandin F2α in progressive MS. Neurology, Neuroimmunology & Neuroinflammation, 3 (4). pp. e256. ISSN 2332-7812 (OA)
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Abstract
OBJECTIVE
We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS).
METHODS
We determined by liquid chromatography-tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2α [PGF2α]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage (neurofilament light protein).
RESULTS
Compared with OND controls, plasma concentrations of F2-isoprostanes and PGF2α were significantly lower in patients with progressive disease, and decreased with increasing disability score (Expanded Disability Status Scale). In contrast, CSF concentrations of PGF2α, but not F2-isoprostanes, were significantly higher in patients with progressive disease than OND controls (p < 0.01). The content of PGF2α in CSF increased with disease severity (p = 0.044) and patient age (p = 0.022), although this increase could not be explained by age. CSF PGF2α decreased with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF2α did not associate with validated CSF markers of inflammation and axonal damage that themselves did not associate with the Expanded Disability Status Scale.
CONCLUSIONS
Our data suggest that MS progression is associated with low systemic oxidative activity. This may contribute to immune dysregulation with CNS inflammation accompanied by increased local cyclooxygenase-dependent lipid oxidation.
| Item Type: | Article |
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| Additional Information: | COPYRIGHT: This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited (https://creativecommons.org/licenses/by-nc-nd/4.0/). The work cannot be changed in any way or used commercially. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Jul 2016 02:27 |
| Last Modified: | 11 Jul 2016 02:30 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/466 |
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