Combination of NEP 1-40 infusion and bone marrow-derived neurospheres transplantation inhibit glial scar formation and promote functional recovery after rat spinal cord injury

Background and Aims: Studies have shown that administration of NEP 1-40, a Nogo-66 receptor antagonist peptide, improves locomotor recovery in rats. We hypothesize that combining NEP 1-40 with another promising therapy, neural stem cell transplantation, might further improve the degree of locomotor recovery. In the present study, we examined whether NEP 1-40 combined with bone marrow stromal cells-derived neurospheres (BMSC-NSs) transplantation would produce synergistic effects on recovery. Material and Methods: Adult Sprague-Dawley rats were subjected to spinal cord injury (SCI) at the T10 vertebral level. Immediately after injury, rats were administrated NEP 1-40 intrathecally for 4 weeks. BrdU-labeled BMSC-NSs (2 x 10(5)) were transplanted into the injured site 7 days after SO. Locomotor recovery was assessed for 10 weeks with BBB scoring. Animals were perfused transcardially 10 weeks after contusion, and histological examinations were performed. Results: The combined therapy group showed statistically better locomotor recovery than the control group at 7 weeks of contusion. Neither of the two single-agent treatments improved locomotor function. The average area of the cystic cavity was significantly smaller in the combined therapy group than in the control group. Fluorescence microscopic analysis showed that NEP 1-40 dramatically inhibited the formation of glial scar and promoted the axons penetration into the scar barrier. Conclusion: This study revealed that BMSC-NSs and NEP 1-40 exhibit synergistic effects on recovery in rat SO. This may represent a potential new strategy for the treatment of SCI.