Abstract
Oligodendrocytes are specialized glial cells that myelinate central nervous system (CNS) axons. Historically, it was believed that the primary role of myelin was to compactly ensheath axons, providing the insulation necessary for rapid signal conduction. However, mounting evidence demonstrates the dynamic importance of myelin and oligodendrocytes, including providing metabolic support to neurons and regulating axon protein distribution. As such, the development and maintenance of oligodendrocytes and myelin are integral to preserving CNS homeostasis and supporting proper functioning of widespread neural networks. Environmental signals are critical for proper oligodendrocyte lineage cell progression and their capacity to form functional compact myelin; these signals are markedly disturbed by injury to the CNS, which may compromise endogenous myelin repair capabilities. This review outlines some key environmental factors that drive myelin formation during development and compares that to the primary factors that define a CNS injury milieu. We aim to identify developmental factors disrupted after CNS trauma as well as pathogenic factors that negatively impact oligodendrocyte lineage cells, as these are potential therapeutic targets to promote myelin repair after injury or disease.
Highlights
The central nervous system (CNS) provides an excellent model to study cellular interactions because of the intimate association of its main parenchyma—neurons and glia
Evidence suggests that Platelet-derived growth factor (PDGF)-A positively modulates OL lineage cells via synergistic effects with components of the extracellular matrix and other pro-proliferation growth factors, such as Fibroblast growth factor 2 (FGF-2) and Insulin-like growth factor-1 (IGF-1), which are upregulated for weeks after spinal cord injury (SCI) [68,164,189,190,191]
Reactive astrocytes in regions of demyelination upregulate CXCL12, which has been proposed to serve as a potent chemoattractant to guide migrating oligodendrocyte precursor cells to the injury site and promote their differentiation [290]
Summary
The central nervous system (CNS) provides an excellent model to study cellular interactions because of the intimate association of its main parenchyma—neurons and glia. Myelin first appeared when animals formed jaws and increased in physical size; myelin allowed increased axon conduction speed, which in turn allowed for faster escape from predators [4]. This huge evolutionary advantage separates vertebrates from invertebrates, who have supporting cells around axons rather than compact myelin [4]. OLs [7,8] Their role in endogenous myelin repair after other types of CNS damage such as trauma is not fully understood. This review will begin by outlining some key factors in normal myelin development and discuss how these and other factors affect the response of OPCs to CNS trauma
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