Neuroprotection by central nervous system remyelination: Molecular, cellular, and functional considerations

Abstract

Oligodendrocytes and their myelin sheaths play an intricate role in axonal health and function. The prevalence of white matter pathology in a wide variety of central nervous system disorders has gained attention in recent years. Remyelination has therefore become a major target of therapeutic research, with the aim of protecting axons from further damage. The axon-myelin unit is elaborate, and demyelination causes profound changes in axonal molecular domains, signal transmission, and metabolism. Remyelination is known to restore some of these changes, but many of its outcomes remain unknown. Understanding how different aspects of the axon-myelin unit are restored by remyelination is important for making effective, targeted therapeutics for white matter dysfunction. Additionally, understanding how subtle deficits relate to axonal function during demyelination and remyelination may provide clues into the impact of myelin on neuronal circuits. In this review, we discuss the current knowledge of the neuroprotective effects of remyelination, as well as gaps in our knowledge. Finally, we propose systems with unique myelin profiles that may serve as useful models for investigating remyelination efficacy. © 2016 Wiley Periodicals, Inc.

Fingolimod Protects Against Ischemic White Matter Damage by Modulating Microglia Toward M2 Polarization via STAT3 Pathway

“…Microglial activation with enhanced release of inflammatory mediators is known to impair myelination in different models of WM injury 2–4 . Here, we found the number of cells positive for the general marker Iba-1 and the phagocytosis marker CD68 were remarkably elevated in BCAS mice, reached the peak on the 10th day after BCAS and then sustained the status of highly activated (Figure 3).…”

“…It has been demonstrated that the neuroinflammation response can contribute to the pathogenesis of ischemic stroke 2, 4, 8, 21 . M2 type microglia have been reported to be an essential part of the regenerative response in CNS demyelinating diseases by promoting oligodendrocyte differentiation 22 .…”

“…White matter (WM) damage manifests as a core pathology in the progression of various diseases such as stroke, vascular dementia, and multiple sclerosis 1, 2 . Characterized by loss of axon-glial integrity and demyelination, WM injury is an important cause of cognitive deficits after cerebral ischemia and is often associated with microglial activation 3 .…”

“…Polarization of microglial populations toward various functional phenotypes can be beneficial or detrimental in response to specific microenvironmental signals following ischemic stroke, which contributes considerably to the regulation of inflammatory status in the injured WM and ultimately impacts the WM integrity 2, 4, 5 . Thus, therapeutic approaches targeting cerebral inflammation should shift from broad suppression of microglia towards the selective balance between their phenotypes in CNS repair after chronic injury.…”

Differential effects of glucose deprivation on the survival of fetal versus adult neural stem cells‐derived oligodendrocyte precursor cells

“…Myelin depletion is a major pathological event in inflammatory diseases, vascular and traumatic lesions of the central nervous system (CNS), and a major cause of consequent neurodegeneration and chronic disabilities in both infants and adults (Verden & Macklin, ). Oligodendrocyte precursor cells (OPCs) are the cells responsible for myelin formation during development, and for myelin turnover and repair during the adult life, thanks to their ability to differentiate into myelinating oligodendrocytes (OLs) (Alizadeh, Dyck, & Karimi‐Abdolrezaee, ).…”