Understanding the NG2 Glial Scar after Spinal Cord Injury

Abstract

NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout the central nervous system and serve as a pool of progenitors to differentiate into oligodendrocytes. In response to spinal cord injury (SCI), NG2 cells increase their proliferation and differentiation into remyelinating oligodendrocytes. While astrocytes are typically associated with being the major cell type in the glial scar, many NG2 cells also accumulate within the glial scar but their function remains poorly understood. Similar to astrocytes, these cells hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit axon regeneration, contribute to the glial-fibrotic scar border, and some even differentiate into astrocytes. Whether NG2 cells also have a role in other astrocyte functions, such as preventing the spread of infiltrating leukocytes and expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not only important for remyelination after SCI but are also a major component of the glial scar with functions that overlap with astrocytes in this region. In this review, we describe the signaling pathways important for the proliferation and differentiation of NG2 cells, as well as the role of NG2 cells in scar formation and tissue repair.

Cell biology of spinal cord injury and repair

“…After CNS injury, NG2-OPCs are present in two compartments, scar borders and spared reactive neural tissue ( Figure 1A and Figure 3A). In scar borders, NG2-OPCs are hypertrophied and are reported to restrict axon dieback and axon regrowth (68)(69)(70). Other reports show that robust axon growth can…”

The diversity and disparity of the glial scar

“…Several developmental signals have been found to be upregulated in the glial scar that promote NG2 glial proliferation and migration to trauma sites: fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), Wnts 27 . However, many NG2 glia in the scar do not differentiate into myelinating oligodendrocytes.…”

Oligodendroglia-lineage cells in brain plasticity, homeostasis and psychiatric disorders

“…Could it also be possible that NG2-glia regulate responsiveness of other cell types in acute stress? Indeed, in animal models of demyelination and CNS injury, several reports demonstrated that NG2-glia cells secrete a variety of pro-inflammatory chemokines and cytokines in pathological conditions that can dampen the glial or neuronal compensation machinery [113,114]…”