Oxidative Stress and Neurobiology of Demyelination

Abstract

Despite a large amount of research which aims at defining the pathophysiology of human demyelination (i.e., multiple sclerosis), etiological bases of disease have been unknown so far. The point of intersection of all assumed etiological factors, which are mainly based upon immunological cascades, is neuroinflammation. The precise definition of the place and role of all pathogenetic factors in the occurrence and development of the disease is of crucial importance for understanding the clinical nature and for finding more effective therapeutic options. There are few studies whose results give more precise data about the role and the importance of other factors in neuroinflammation, besides immunological ones, with regard to clinical and paraclinical correlates of the disease. The review integrates results found in previously performed studies which have evaluated oxidative stress participation in early and late neuroinflammation. The largest number of studies indicates that the use of antioxidants affects the change of neuroinflammation course under experimental conditions, which is reflected in the reduction of the severity and the total reversibility in clinical presentation of the disease, the faster achieving of remission, and the delayed and slow course of neuroinflammation. Therapies based on the knowledge of redox biology targeting free radical generation hold great promise in modulation of the neuroinflammation and its clinical presentations.

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

“…It is possible that a new target of treatment will focus on neutralizing free radicals. The course of the disease is affected by the use of antioxidants and substances that affect antioxidant pathways which reduce the severity and cause faster remission and less pronounced course of neuroinflammation and neurodegeneration [76, 91]. …”

Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant

“…These results indicate that while oxidized lipids may not feature in the initial activation of immune cells, they may well play a central role in the subsequent demyelination, as previously suggested. 45 Since oxidized lipoproteins are neurotoxic and have proinflammatory properties, lipid peroxidation products could be involved in demyelination and axonal injury in MS. 46,47 In addition, the activity of Nano-PSO, at least at the particle size shown to be beneficial for EAE, may be mostly confined to the CNS, thereby interfering with brain oxidation features and demyelination and less with inhibition of infiltration. Owing to the lack of toxicity of these reagents, Nano-PSO may be a good choice for individuals at initial stages of demyelinating diseases such as MS. At later stages, Nano-PSO may be used in combination with advanced MS treatments such as Natalizumab (Tysabri), which reduces the migration of lymphocytes to the CNS by binding to the α4 integrin very late antigen, 48 or in combination of other antioxidant formulations.…”

On elucidation of the role of mitochondria dysfunction and oxidative stress in multiple sclerosis

“…Aside from MtD, OS plays a role in demyelination and axonal damage in MS . Findings from several studies have suggested that OS plays the most important role in the demyelination and neurodegeneration observed in MS . OS causes selective oligodendrocyte death and can disrupt the process of oligodendrocyte differentiation, leading to demyelination .…”

“…34 Also, MtD has been found to play a key role in a progressive axonal loss in MS. 17,35,36 Following axonal demyelination in MS, it has been hypothesized that mitochondria play a greater role in maintaining axonal function as an adaptive process to the increased energy need of demyelinated axons but MtD results over time leading to severe and chronic axonal damage. 35,37,38 F I G U R E 1 The role of mitochondria dysfunction and oxidative stress in MS | 307 TOBORE Aside from MtD, OS plays a role in demyelination and axonal damage in MS. [39][40][41][42] Findings from several studies have suggested that OS plays the most important role in the demyelination and neurodegeneration observed in MS. [42][43][44][45][46] OS causes selective oligodendrocyte death and can disrupt the process of oligodendrocyte differentiation, leading to demyelination. 47,48 Damage from OS on oligodendrocytes and neurons has been found to be associated with active demyelination and axonal or neuronal damage in MS. 42 Studies have revealed that OS modulates OPC signal processes which are vital for OPC proliferation and differentiation resulting in hypomyelination.…”