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.
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.
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DOI：
10.4103/0028-3886.84341
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发表时间：
2011-07
期刊：
影响因子：
2.7
通讯作者：
Zhou Zhilai;Z. Hui;Chen Yinhai;Chengju Zhong;Min Shaoxiong;Yu Bo;J. An-min
中科院分区：
文献类型：
--
作者：
Zhou Zhilai;Z. Hui;Chen Yinhai;Chengju Zhong;Min Shaoxiong;Yu Bo;J. An-min
背景和目的 研究表明，给予 NEP1-40（一种 Nogo-66 受体拮抗剂肽）可改善大鼠的运动恢复。我们假设将 NEP1-40 与另一种有前景的疗法（神经干细胞移植）相结合，可能会进一步提高运动恢复程度。在本研究中，我们检查了NEP1-40联合骨髓基质细胞源性神经球（BMSC-NSs）移植是否会对恢复产生协同作用。材料和方法 成年 Sprague-Dawley 大鼠在 T10 椎骨水平遭受脊髓损伤 (SCI)。损伤后立即对大鼠进行鞘内注射NEP1-40，持续4周。 SCI后7天将BrdU标记的BMSC-NSs（2×105）移植到损伤部位。使用 BBB 评分评估 10 周的运动恢复情况。挫伤后10周对动物进行心脏灌注，并进行组织学检查。结果 挫伤 7 周时，联合治疗组的运动恢复情况在统计学上优于对照组。两种单药治疗均未改善运动功能。联合治疗组的囊腔平均面积明显小于对照组。荧光显微镜分析表明NEP1-40显着抑制神经胶质疤痕的形成并促进轴突穿透疤痕屏障。结论 这项研究表明，BMSC-NS 和 NEP 1-40 对大鼠 SCI 的恢复具有协同作用。这可能代表了治疗 SCI 的潜在新策略。
BACKGROUND AND AIMS Studies have shown that administration of NEP1-40, a Nogo-66 receptor antagonist peptide, improves locomotor recovery in rats. We hypothesize that combining NEP1-40 with another promising therapy, neural stem cell transplantation, might further improve the degree of locomotor recovery. In the present study, we examined whether NEP1-40 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 NEP1-40 intrathecally for 4 weeks. BrdU-labeled BMSC-NSs (2×105 ) were transplanted into the injured site 7 days after SCI. 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 NEP1-40 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 SCI. This may represent a potential new strategy for the treatment of SCI.