A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats.

A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats.
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DOI:
10.1016/j.expneurol.2010.12.020
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发表时间:
2012-02
影响因子:
5.3
通讯作者:
Steward, Oswald
Steward, Oswald
中科院分区:
医学2区
文献类型:
--
作者:
Sharp, Kelli G.;Flanagan, Lisa A.;Yee, Kelly Matsudaira;Steward, Oswald

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这项研究是作为NIH“研究设施-脊髓损伤”项目的一部分进行的,以支持独立复制已发表的研究。在这里,我们重复了一项研究,报告了一个组合治疗与雪旺细胞移植,Rolipram全身递送,以提高环AMP水平,和脊髓内注射二丁酰环AMP增强运动恢复大鼠在胸部水平的挫伤后。我们比较了以下实验组:1)接受雪旺细胞移植,系统性Rolipram和注射db-环AMP的大鼠2)仅接受雪旺细胞移植并植入空泵的大鼠作为对照; 3)仅接受咯利普兰并植入空泵作为对照的大鼠,以及4)除了将DMEM注射到脊髓中并植入空泵之外不接受治疗的对照大鼠。Pearse等人报告的主要结果未得到重现,因为联合治疗组在任何指标上均未表现出更大的恢复,尽管仅接受雪旺细胞的组在几项结局指标上表现出恢复增强。联合治疗的失败可能部分是由于在我们的研究中与Pearse et al.相比,许旺细胞植入不太成功。讨论了与复制失败相关的问题,特别是当效应量较小时。
This study was undertaken as part of the NIH “Facilities of Research-Spinal Cord Injury” project to support independent replication of published studies. Here, we repeated a study reporting that a combinatorial treatment with transplants of Schwann cells, systemic delivery of Rolipram to enhance cyclic AMP levels, and intra-spinal injections of dibutyryl cyclic AMP enhanced locomotor recovery in rats after contusion injuries at the thoracic level. We compared the following experimental groups: 1) rats that received Schwann cell transplants, systemic Rolipram, and injections of db-cyclic AMP (the combined treatment group that showed the greatest improvement in function); 2) rats that received Schwann cell transplants only and implantation of empty pumps as control; 3) rats that received Rolipram only and implantation of empty pumps as control, and 4) control rats that received no treatment other than the injection of DMEM into the spinal cord and implantation of empty pumps. The principal findings reported in Pearse et al. were not replicated in that the combined treatment group did not exhibit greater recovery on any of the measures, although the group that received Schwann cells only did exhibit enhanced recovery on several of the outcome measures. The failure of the combined treatment may be due in part to less successful engraftment of Schwann cells in our study vs. Pearse et al. Issues relating to failures to replicate, especially when effect size is small, are discussed.
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