gms | German Medical Science

Objective: Neural precursor cell (NPC) transplantation after spinal cord injury (SCI) has shown beneficial effects on neuroregeneration. Functional recovery, however, is limited due to inflammation, astrogliosis and cyst-formation as well as tissue scarring. Treadmill training (TT) following SCI might reduce these detrimental effects. We therefore examined histological changes with a possible impact on functional recovery in rats, who received a combined treatment of NPCs and TT after cervical SCI.

Methods: 43 Wistar rats were subjected to cervical clip-contusion/compression injury at C6. Animals were randomized into four treatment groups (NPC + TT, NPC only, vehicle, sham). NPCs were injected into the spinal cord of immunosuppressed rats 10 days after SCI. In addition, growth factors were intrathecally infused for seven days. Daily TT was initiated 48 hours after NPC transplantation and weekly neurobehavioral tests were executed. Eight weeks after SCI, animals were sacrificed, immunohistological analyses were performed and results statistically analyzed (p < 0.05 was considered significant).

Results: Animals having received additional TT showed significantly more surviving NPCs and a significantly higher number of the cells differentiated into oligodendrocytes. Tissue scarring (CSPG) and cyst size (GFAP) were significantly decreased compared to the NPC alone and vehicle groups. Astrogliosis and inflammation were significantly reduced in both, the NPC + TT and NPC only groups compared to the vehicle group. Analysis of neurological outcome revealed faster recovery and higher BBB scores in NPC + TT animals compared to animals in the NPC only and vehicle group. CatWalk gait analysis showed significant improvement of print area as well as swing speed in NPC + TT animals compared to the other groups. Correspondingly, those animals also showed significantly less stepping errors in the Gridwalk test 8 weeks after SCI.

Conclusion: In our study, the addition of TT to NPC transplantation led to higher survival and increased differentiation of NPCs. Furthermore, detrimental effects of SCI such as cyst size and tissue scarring which limit neuroregeneration after NPC therapy were reduced when TT was performed. Accordingly, functional recovery was improved in animals with NPC + TT. In summary, our data suggest that TT might be beneficial in addition to NPC transplantation in the treatment of cervical SCI.