Oxidative Stress Induced by Lipid Peroxidation Is Related with Inflammation of Demyelination and Neurodegeneration in Multiple Sclerosis

Abstract

Background: Multiple sclerosis (MS) is a chronic autoimmune demyelination disorder of the central nervous system (CNS) and its etiology remains unknown. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines, which contribute to the development and progression of multiple sclerosis. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress is involved in the inflammation leading demyelination and neurodegeneration in the pathogenesis of multiple sclerosis. Summary: The present study aims to determine two biochemical markers of oxidative stress: TAC and MDA and to show their correlations whether oxidative stress reaction occurs in the demyelination through analyzing samples including peripheral blood and cerebrospinal fluid (CSF) from patients with relapsing-remitting MS (RR-MS). Totally, there were 20 patients in the control groups made from individuals with normal pressure hydrocephalus. Thirty MS patients diagnosed with McDonald diagnostic criteria (2010) treated with methylprednisolone were included in this study. Data were stratified by the degree of severity in order to clarify the role of oxidative stress in the mechanisms of MS and to assess its potential as a biomarker. Thirty clinically definite RRMS patients were enrolled in this study. Levels of MDA, GSH, total antioxidant capacity TAC, GSH-Px and ROS, were determined in serum of the control group and RRMS patients in 7 days before MP (methylprednisolone) treatment and one month after MP treatment. Statistical analysis was performed with one-way analysis of variance (ANOVA), followed by LSD's post hoc tests. Key Messages: Oxidative stress precedes the inflammatory response in the multiple sclerosis patients. And methylprednisolone treatment can decrease brain antioxidant enzymes to reduce the neuroinflammatory attack.

Hyperpolarized 13 C MR metabolic imaging can detect neuroinflammation in vivo in a multiple sclerosis murine model

“…For instance, after W6 of CPZ administration we observed a strong reduction of MPs in the corpus callosum. Although most of the remaining MPs still express PDK1 and there is a trend toward decreased PDH activity compared with CTRL, we did not detect a significantly increased production of HP [1][2][3][4][5][6][7][8][9][10][11][12][13] C]lactate at that time point, which may be explained by the limited sensitivity of HP 13 C MRSI to lower MP number. Furthermore, the lack of increase in the HP [1-13 C]lactate-topyruvate ratios in two of seven mice at W4 (Fig.…”

“…In the vast majority of cases, demyelinating lesions present a high inflammatory component, with elevated density of activated microglia/macrophages (mononuclear phagocytes, MPs) (4-6). Importantly, evidence suggests that proinflammatory MPs are one of the most abundant sources of reactive oxygen species (7), which mediate demyelination and axonal injury (8). Due to their central role in MS pathogenesis, noninvasive imaging of proinflammatory MPs would be of high importance for monitoring progression and response to antiinflammatory therapeutic approaches.…”

Ion mobility-enhanced MSE-based label-free analysis reveals effects of low-dose radiation post contextual fear conditioning training on the mouse hippocampal proteome

“…Deposition or loss of the myelin sheath results in irreversible axonal degeneration and affects neuronal connectivity [73]. Defective myelination, due to either genetic or acquired factors, can lead to neurological diseases including multiple sclerosis [74], leukodystrophies [75], and peripheral neuropathies [76]. Exposure to high dose of X-ray radiation reduced the numbers of migratory neuroblasts, and significantly less brain myelination was observed as well [77].…”

Novel Approaches of Oxidative Stress Mechanisms in the Multiple Sclerosis Pathophysiology and Therapy

“…Wang et al examined levels of MDA and TAC in peripheral blood and in the CSF of RRMS patients 7 days before methylprednisolone (MP) treatment and 1 month after MP treatment. They found that the increase in OS markers precedes inflammatory response in MS patients and MP treatment reduces the neuroinflammatory attack by decreasing brain antioxidant enzymes (111). Ozone autohemotherapy is an emerging therapeutic technique that can change brain metabolism.…”