The central canal (CC) of the spinal cord is a neurogenic niche consisting of quiescent neural stem cells (NSCs) capable of responding to traumatic damage to the spinal cord by increasing their proliferative activity and sending migrating progeny toward the site of injury, where they contribute to the formation of the glial scar. However, CC NSCs have been demonstrated to have the capability to differentiate into all neural lineage cells in vitro , but also in vivo , in response to infusion of specific growth factors that promote neuronal induction after injury, as well as when transplanted into other neurogenic niches, such as the subgranular zone of the hippocampus. This suggests that CC NSCs may represent a recruitable endogenous source of neural lineage cells that could be harnessed to replenish damaged or lost neural tissue after traumatic spinal cord injury (SCI).
NSCs isolated from the CC neurogenic niche of uninjured rats and mice have been shown to display limited proliferative capacity in vitro , with significantly greater proliferative activity achieved with NSCs isolated from SCI-lesioned rats and mice indicating an injury-specific activation of the quiescent CC NSC pool. A central question that currently remains unanswered is whether, and to what extent the CC niche can spontaneously generate viable neurons, and act as a potential source of new cells to replace lost neuronal populations in situ , and whether SCI sequalae impact future NSC neurogenic potential. To address this question, we need to understand whether the nature of the injury plays a role in the CC neurogenic niche response. In this study, we compared the intrinsic proliferative response and neurogenic potential of NSCs harvested from the CC neurogenic niche in adult female Sprague Dawley rats by culturing said NSCs across three conditions; (i) control, i.e., uninjured tissue, (ii) after in vivo compression injury 3 days before harvesting, and (iii) after in vivo simulated burst fracture injury 3 days before harvesting in vitro . We found that lacerations of the dura mater surrounding the spinal cord during a compression injury resulted in drastically altered and persistent in vitro NSC behavior encompassing both proliferation and development compared to uninjured control and compression injury with the dura intact.