Abstract
BackgroundSpinal cord injury (SCI) is a devastating condition mainly deriving from a traumatic damage of the spinal cord (SC). Immune cells and endogenous SC-neural stem cells (SC-NSCs) play a critical role in wound healing processes, although both are ineffective to completely restore tissue functioning. The role of SC-NSCs in SCI and, in particular, whether such cells can interplay with the immune response are poorly investigated issues, although mechanisms governing such interactions might open new avenues to develop novel therapeutic approaches.MethodsWe used two transgenic mouse lines to trace as well as to kill SC-NSCs in mice receiving SCI. We used Nestin CreERT2 mice to trace SC-NSCs descendants in the spinal cord of mice subjected to SCI. While mice carrying the suicide gene thymidine kinase (TK) along with the GFP reporter, under the control of the Nestin promoter regions (NestinTK mice) were used to label and selectively kill SC-NSCs.ResultsWe found that SC-NSCs are capable to self-activate after SCI. In addition, a significant worsening of clinical and pathological features of SCI was observed in the NestinTK mice, upon selective ablation of SC-NSCs before the injury induction. Finally, mice lacking in SC-NSCs and receiving SCI displayed reduced levels of different neurotrophic factors in the SC and significantly higher number of M1-like myeloid cells.ConclusionOur data show that SC-NSCs undergo cell proliferation in response to traumatic spinal cord injury. Mice lacking SC-NSCs display overt microglia activation and exaggerate expression of pro-inflammatory cytokines. The absence of SC-NSCs impaired functional recovery as well as neuronal and oligodendrocyte cell survival. Collectively our data indicate that SC-NSCs can interact with microglia/macrophages modulating their activation/responses and that such interaction is importantly involved in mechanisms leading tissue recovery.
Highlights
Spinal cord injury (SCI) is a devastating condition mainly deriving from a traumatic damage of the spinal cord (SC)
The reporter GFP was expressed in the ependymal cells of the central canal, while not expressed in parenchymal cells and in particular in endothelial cells that in the brain are known to be positive for Nestin
This result confirmed previous observation showing that the use of the II intron enhancer of the Nestin promoter restricts the transgene expression to neural stem cell (NSC) [30]
Summary
Spinal cord injury (SCI) is a devastating condition mainly deriving from a traumatic damage of the spinal cord (SC). Neural stem cell (NSC)-based treatments have received a great deal of Cusimano et al Journal of Neuroinflammation (2018) 15:58 is lining the central canal of the SC, arranged in specific germinal niches. Such niches show a different cytoarchitecture, if compared with niches of the brain subventricular zone (SVZ), [6, 7]. A fraction of SC-NSCs express Olig-2 and acquire the cell morphology of immature oligodendrocytes that eventually migrate to the injury site Later on, such cells differentiate in myelinating oligodendrocytes that enwrap axons [10, 11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
