Absence of systemic oxidative stress and increased CSF prostaglandin F in progressive MS

Magda Lam, Ghassan Maghzal, Mohsen Khademi, Fredrik Piehl, Rikke Ratzer, Jeppe Romme Christensen, Finn Thorup Sellebjerg, Tomas Olsson, Roland Stocker

Research output: Contribution to journalArticle

12 Citations (Scopus)
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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 F [PGF]) 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 PGF were significantly lower in patients with progressive disease, and decreased with increasing disability score (Expanded Disability Status Scale). In contrast, CSF concentrations of PGF, but not F2-isoprostanes, were significantly higher in patients with progressive disease than OND controls (p < 0.01). The content of PGF 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 PGF decreased with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF 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.
Original languageEnglish
Article numbere256
Pages (from-to)1-9
Number of pages9
JournalNeurology: Neuroimmunology and Neuroinflammation
Volume3
Issue number4
DOIs
Publication statusPublished - Aug 2016
Externally publishedYes

Bibliographical note

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Keywords

  • Isoprostane
  • progressive multiple sclerosis
  • Neurological disease
  • prostaglandin F2a
  • Reactive oxygen species

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    Lam, M., Maghzal, G., Khademi, M., Piehl, F., Ratzer, R., Romme Christensen, J., ... Stocker, R. (2016). Absence of systemic oxidative stress and increased CSF prostaglandin F in progressive MS. Neurology: Neuroimmunology and Neuroinflammation, 3(4), 1-9. [e256]. https://doi.org/10.1212/NXI.0000000000000256