Dynamic Diversity of Glial Response Among Species in Spinal Cord Injury

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.

Keywords: glial bridge; glial cells; glial scar; immune cells; primates; regenerative species; rodents; spinal cord injury (SCI).

FIGURE 1

Cellular dynamics after spinal cord injury. (A) Immune cell infiltration patterns in mice (plain lines) and rats (dashed lines). (B) Glial cell numbers in rodents (plain lines) and primates (dashed lines). For each cell type, both graphs represent the number of cells over time, relative to their maximum value.

FIGURE 2

Glial scar formation after spinal cord injury in rodents and primates. (A) Acute stage. Cellular infiltration, reactivity, proliferation, and edema at the lesion site. (B) Glial scar stabilisation at the subacute/chronic stage. Note the substantial role of scarring astrocytes in separating the lesion core from spared tissues.

FIGURE 3

The glial bridge after spinal cord injury in species with high regenerative capacities and perinatal mammals. (A) Tissue clearance, glial bridge, and axon sprouting at the acute/subacute stage. Arrows represent the involvement of radial glia in the glial bridge formation. (B) Remyelination and return to homeostasis at the chronic stage.