**3. Reactive oxygen species, cytokines, and axonal damage in multiple sclerosis**

Mechanisms of axonal damage are the consequence of the presence of TNF‐α, matrix metal‐ loproteinases (MMPs), ROS, antibodies, increased glutamate, and aspartate, and these molecules cause excitotoxicity in MS patients. Glutamate is increased in MS patients (active lesions) especially in white matter of normal appearance. Mature oligodendrocytes and astrocytes are highly sensitive to glutamate due to the expression of AMPA and NMDA receptors [9]. The myelin sheath can be damaged by cytokines, autoantibodies, ROS, proteo‐ lytic enzymes, and phagocytosis. Increased ROS by activated microglia (specialized macro‐ phages of the CNS) during the immune response gives a state of increased lipid peroxidation, and the oligodendrocyte cell is the cell most susceptible to damage by ROS. Myelin degradation may be the result of lipid peroxidation mediated by peroxides, but the role of these specific toxic factors in the pathogenesis of MS remains partially elusive [9].
