gms | German Medical Science

Objective: Traumatic spinal cord injury (SCI) is a devastating event with limited functional recovery. As a potential treatment approach, neural precursor cell (NPC) transplantation has shown beneficial effects on neuroregeneration. However, survival and differentiation of transplanted NPCs and thus functional recovery remain limited. The Sonic Hedgehog (SHH) pathway might play a protective role after CNS injury. We, therefore, investigated the effects of intrathecal SHH administration on transplanted NPCs as well as the impact of a combined treatment approach on neuroregeneration after thoracic SCI in rats.

Methods: 37 Wistar rats were subjected to thoracic clip-contusion/compression SCI at Th10. Animals were randomized into five treatment groups (SHH only, NPC only, SHH+NPC, Vehicle, Sham). NPCs were injected into the spinal cord of immunosuppressed rats seven days after SCI. During the same surgery, an osmotic pump was implanted and the intrathecal administration of SHH was initiated and continued for seven days. To assess functional recovery, the BBB score, the Gridwalk test as well as the CatWalk gait analysis were performed weekly. Animals were sacrificed 38 days after SCI and immunohistological analyses were conducted. Results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant).

Results: The administration of SHH alone led to significant improvements in neuroinflammation (less invasion of T-lymphocytes, M1-macrophages and microglia) as well as astrogliosis while the impact of NPC-transplantation alone on such postinjury changes was limited. However, in contrast to SHH only animals, NPC only animals showed improved functional recovery when compared to Vehicle animals. When SHH-administration and NPC-transplantation were combined, neuroinflammation as well as the rates of apoptosis, and preserved tissue were significantly improved compared to each individual treatment. Moreover, the addition of SHH-administration to NPC-transplantation led to higher survival of NPCs and increased NPC-differentiation into adult neurons and oligodendrocytes. Finally, with the combined treatment approach, animals showed the highest functional recovery 38 days after SCI.

Conclusion: In our study, a combined treatment approach with intrathecal SHH-administration and NPC-transplantation showed the highest improvements of neuroregeneration on the cellular as well as the functional level 38 days after thoracic SCI.