Abstract
Inflammation after traumatic spinal cord injury (SCI) is non-resolving and thus still present in chronic injury stages. It plays a key role in the pathophysiology of SCI and has been associated with further neurodegeneration and development of neuropathic pain. Neural precursor cells (NPCs) have been shown to reduce the acute and sub-acute inflammatory response after SCI. In the present study, we examined effects of NPC transplantation on the immune environment in chronic stages of SCI. SCI was induced in rats by clip-compression of the cervical spinal cord at the level C6-C7. NPCs were transplanted 10 days post-injury. The functional outcome was assessed weekly for 8 weeks using the Basso, Beattie, and Bresnahan scale, the CatWalk system, and the grid walk test. Afterwards, the rats were sacrificed, and spinal cord sections were examined for M1/M2 macrophages, T lymphocytes, astrogliosis, and apoptosis using immunofluorescence staining. Rats treated with NPCs had compared to the control group significantly fewer pro-inflammatory M1 macrophages and reduced immunodensity for inducible nitric oxide synthase (iNOS), their marker enzyme. Anti-inflammatory M2 macrophages were rarely present 8 weeks after the SCI. In this model, the sub-acute transplantation of NPCs did not support survival and proliferation of M2 macrophages. Post-traumatic apoptosis, however, was significantly reduced in the NPC group, which might be explained by the altered microenvironment following NPC transplantation. Corresponding to these findings, reactive astrogliosis was significantly reduced in NPC-transplanted animals. Furthermore, we could observe a trend toward smaller cavity sizes and functional improvement following NPC transplantation. Our data suggest that transplantation of NPCs following SCI might attenuate inflammation even in chronic injury stages. This might prevent further neurodegeneration and could also set a stage for improved neuroregeneration after SCI.
Highlights
Cervical spinal cord injury (SCI) is a devastating event with severe consequences for patients including paralysis, autonomic dysfunctions, and sensory deficits
We examined the effects of Neural precursor cells (NPCs) transplantation on the immune environment at chronic stages of a clinically highly relevant cervical (C6-C7) SCI model
Surviving NPCs differentiated primarily along the oligodendroglial lineage (994.32 ± 199.03 green fluorescent protein (GFP)+/Adenomatous Polyposis Coli (APC)+), while only a minority of NPCs differentiated into neurons (91.91 ± 24.02 GFP+/NeuN+; Figure 1C)
Summary
Cervical spinal cord injury (SCI) is a devastating event with severe consequences for patients including paralysis, autonomic dysfunctions, and sensory deficits. Less than 1% of spinal cord injury patients regain a normal neurological status by the time they are discharged from the hospital, and therapeutic options are still very limited [1, 2]. The cervical spine is involved in 54% of spinal cord injuries—by far more often than any other region of the spine [1]. Traumatic SCI induces an inflammatory response that includes immune cell infiltration, up-regulation of inflammatory cytokines and production of oxygen/nitrogen radicals [3, 4]. Some beneficial effects have been described, the resulting inflammatory milieu is regarded to impede neuroregeneration and to exacerbate secondary spinal cord damage [5]. Post-traumatic inflammation is nonresolving and persists in chronic stages of SCI [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
