Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

Abstract

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. 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 the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

Multiple Sclerosis: Effect of Oral Administration of an Antioxidant Dietary Supplement in C57BL6/N Induced Model of Experimental Autoimmune Encephalomyelitis

“…The oxidation-reduction thus triggered (redox cycling) precisely lead to the formation of ROS, such as the hydroxyl radical is particularly active in the initiation of lipid peroxidation. Similar phenomena of redox cycling seem to participate in the pathogenesis of hitting in MS [18]. Moreover, complex interactions, in degenerative processes, involve also glutathione, the NO and dopamine, which have the same ability to catalyze reactions of redox cycling of iron and copper.…”

Inflammation in the spotlight—clinical relevance of genetic variants affecting nuclear factor κB and tumor necrosis factor receptor 1

“…An alternative hypothesis proposes that MS is a neurodegenerative process exacerbated by sustained inflammatory activity (5). Being considered upstream to the primary activation of these disturbances, NF-κB is recognized as a proinflammatory cytokine response element located at the forefront of such impairment, according to its role into inflammatory pathways, controlling the activation, proliferation, and cytokine release following immune response, including (but not limited to) the focal inflammatory demyelinating lesions that, in MS, are characterized by perivascular infiltrates containing monocytes, a significant number of macrophages, and both T and B cells (6).…”

Application of nanomedicine for crossing the blood–brain barrier: Theranostic opportunities in multiple sclerosis

“…These sequential events may describe the initial stages of MS occurrence, suggesting a mechanism by which crosstalk between the circulation and the brain can lead to disruption of the BBB. It has been shown that oxidative stress significantly increases the production and function of matrix metallopeptidase (MMP)-2 and -9 in endothelial cells and macrophages (Yazdani et al 2011;Ortiz et al 2013;Mirshafiey et al 2014). The increased levels of these enzymes have been reported in astrocytes in MS lesions (Cuzner et al 1996).…”