gms | German Medical Science

Objective: Posttraumatic inflammation after spinal cord injury (SCI) is non-resolving and still present in chronic injury stages. It is thought to play a key role in the pathophysiology of SCI and has been associated with further neurodegeneration and impaired functional recovery. Neural Precursor Cells (NPCs) have been shown to reduce the acute und sub-acute inflammatory response after SCI in animal models. In the present study, we examined effects of NPC transplantation on the chronic immune environment after cervical SCI in rats.

Methods: 22 Wistar rats received a cervical clip-contusion/compression SCI at the C6 level. Animals were randomized into a treatment (NPC) and control (vehicle) group and NPCs were intramedullary injected 10 days after SCI. Animals were immunosuppressed and received intrathecal infusion of growth factors via an osmotic pump for seven days. Functional outcome was assessed weekly for 8 weeks using the BBB score, before animals were sacrificed. Immunofluorescence analysis of M1/M2-macrophages, T-lymphocytes, astrogliosis, and apoptosis was performed on frozen spinal cord sections. Results were statistically analyzed (p < 0.05 was considered significant).

Results: Rats treated with NPC treatment had significantly fewer pro-inflammatory M1-macrophages and reduced immunodensity for iNOS, its marker enzyme, compared to the control group at the chronic inflammatory state 8 weeks after SCI. At the same time, anti-inflammatory M2-macrophages were barely present and sub-acute transplantation of NPCs therefore did not induce M2 conservation or propagation. Post-traumatic apoptosis, however, was significantly reduced in the NPC group, which might be explained by the attenuated microenvironment following NPC transplantation. Furthermore, a trend towards reduced astrogliosis, smaller cyst size and functional improvement in the BBB score could be observed following NPC transplantation.

Conclusion: Our data suggests that sub-acute transplantation of NPCs following cervical SCI in rats attenuates chronic inflammation even in chronic injury stages. This might prevent further neurodegeneration and could set the stage for improved neuroregeneration after SCI.