Abstract
The glial scar that forms after traumatic spinal cord injury (SCI) is mostly composed of microglia, NG2 glia, and astrocytes and plays dual roles in pathophysiological processes induced by the injury. On one hand, the glial scar acts as a chemical and physical obstacle to spontaneous axonal regeneration, thus preventing functional recovery, and, on the other hand, it partly limits lesion extension. The complex activation pattern of glial cells is associated with cellular and molecular crosstalk and interactions with immune cells. Interestingly, response to SCI is diverse among species: from amphibians and fishes that display rather limited (if any) glial scarring to mammals that exhibit a well-identifiable scar. Additionally, kinetics of glial activation varies among species. In rodents, microglia become activated before astrocytes, and both glial cell populations undergo activation processes reflected amongst others by proliferation and migration toward the injury site. In primates, glial cell activation is delayed as compared to rodents. Here, we compare the spatial and temporal diversity of the glial response, following SCI amongst species. A better understanding of mechanisms underlying glial activation and scar formation is a prerequisite to develop timely glial cell-specific therapeutic strategies that aim to increase functional recovery.
Highlights
Traumatic injuries, including spinal cord injury in the adult mammalian central nervous system, induce a glial response that eventually forms a glial scar that is largely occupied by microglia, NG2 glia and astrocytes
Within areas undergoing Wallerian degeneration, following dorsal funiculotomy, oligodendrocyte density (Olig2) decreased at subacute (10 days) and chronic (30 days) stages, Olig2+ cells were still present (Wang et al, 2009). These results demonstrate that the glial response to spinal cord injury (SCI) exhibits similar dynamics in rats and mice; the immune cell response occurs earlier in rats than in mice (Figures 1A,B)
Responses of glial and immune cells following spinal cord injury display similarities and differences across species that are strongly correlated with functional recovery
Summary
Traumatic injuries, including spinal cord injury in the adult mammalian central nervous system, induce a glial response that eventually forms a glial scar that is largely occupied by microglia, NG2 glia and astrocytes. Analysis of activated microglia/macrophages revealed that, from 3 to 12 months post-injury, few cells were located in the core of the lesion as compared to the glial scar (Camand et al, 2004). Using RNAseq of microglia/macrophages (CX3CR1+ cells), following partial and complete spinal cord section, we have shown that microglial activation is dependent on the time post-injury but not on the lesion severity (Noristani et al, 2017).
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