Oxidative Stress Markers in Cerebrospinal Fluid of Newly Diagnosed Multiple Sclerosis Patients and Their Link to Iron Deposition and Atrophy

Abstract

Oxidative stress has been implied in cellular injury even in the early phases of multiple sclerosis (MS). In this study, we quantified levels of biomarkers of oxidative stress and antioxidant capacity in cerebrospinal fluid (CSF) in newly diagnosed MS patients and their associations with brain atrophy and iron deposits in the brain tissue. Consecutive treatment-naive adult MS patients (n = 103) underwent brain MRI and CSF sampling. Healthy controls (HC, n = 99) had brain MRI. CSF controls (n = 45) consisted of patients with non-neuroinflammatory conditions. 3T MR included isotropic T1 weighted (MPRAGE) and gradient echo (GRE) images that were processed to quantitative susceptibility maps. The volume and magnetic susceptibility of deep gray matter (DGM) structures were calculated. The levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-iso prostaglandin F2α (8-isoPG), neutrophil gelatinase-associated lipocalin (NGAL), peroxiredoxin-2 (PRDX2), and malondialdehyde and hydroxyalkenals (MDA + HAE) were measured in CSF. Compared to controls, MS patients had lower volumes of thalamus, pulvinar, and putamen, higher susceptibility in caudate nucleus and globus pallidus, and higher levels of 8-OHdG, PRDX2, and MDA + HAE. In MS patients, the level of NGAL correlated negatively with volume and susceptibility in the dentate nucleus. The level of 8-OHdG correlated negatively with susceptibility in the caudate, putamen, and the red nucleus. The level of PRDX2 correlated negatively with the volume of the thalamus and both with volume and susceptibility of the dentate nucleus. From MRI parameters with significant differences between MS and HC groups, only caudate susceptibility and thalamic volume were significantly associated with CSF parameters. Our study shows that increased oxidative stress in CSF detected in newly diagnosed MS patients suggests its role in the pathogenesis of MS.

Peroxiredoxin 2 Is a Potential Objective Indicator for Severity and the Clinical Status of Subarachnoid Hemorrhage Patients

“…The essence of Prx2 is a peroxidase encoded by the Prdx2 gene [ 14 ], which has the effect of decomposing reactive oxygen species (ROS) [ 15 ]. In our earlier study, we determined the protective effect of Prx2 in animal experiments.…”

CSF Markers of Oxidative Stress Are Associated with Brain Atrophy and Iron Accumulation in a 2-Year Longitudinal Cohort of Early MS

“…In our previous cross-sectional study on this cohort, we observed increased CSF levels of PRDX2 that correlated with thalamic atrophy in MS patients. This highlighted the active role of anti-oxidative cytoprotective enzymes in the termination of the inflammatory reaction [ 3 , 32 ]. The lack of association between PRDX2 and other markers of oxidative stress with the degree of volume loss in the longitudinal study may be theoretically related to the positive effect of anti-inflammatory treatment on oxidative stress in MS [ 30 , 33 ].…”

“…Healthy controls (HC) were recruited from the general community [ 3 , 45 ]. The controls were free of neurologic or other medical disorders affecting the brain and had a normal neurological examination.…”

“…The aberrant immunological response is reflected in the cerebrospinal fluid (CSF). Increased levels of markers of brain tissue degradation, astrocytic activation, oxidative stress, and lipid peroxidation have been identified in the CSF of MS patients, even at the onset of the disease [ 2 , 3 ]. Neurofilament light chain (NfL), which reflects neuro-axonal damage, has been studied as a biomarker of disease activity [ 4 , 5 ].…”

“…Neurofilament light chain (NfL), which reflects neuro-axonal damage, has been studied as a biomarker of disease activity [ 4 , 5 ]. Increased levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), peroxiredoxin-2 (PRDX2), and malondialdehyde and hydroxyalkenals (MDA+HAE), as markers of oxidative stress and lipid oxidation, have been identified in treatment naïve MS patients [ 3 , 6 ].…”