OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats
OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats
复制标题
DOI：
10.1093/brain/awm267
复制
发表时间：
2008-01-01
期刊：
影响因子：
14.5
通讯作者：
Phelps, Patricia E.
中科院分区：
文献类型：
--
作者：
Kubasak, Marc D.;Jindrich, Devin L.;Phelps, Patricia E.
许多脊髓损伤的治疗策略寻求最大限度地恢复功能，其中两种策略显示出实质性的前景：嗅球来源的嗅鞘胶质细胞(OEG)移植和跑步机踏步训练。在这项研究中，我们重新研究了OEG植入术的有效性问题，但使用客观、定量的运动表现测量来测试长期阶梯训练和嗅球衍生OEG植入术是否存在互补效应。我们研究了完整的成年雌性大鼠胸中段脊髓横断，并比较了四个实验组：未训练组、训练组、未训练组和训练组。为了评估横断后4个月和7个月后后肢运动恢复的程度，我们使用了三个量化步进能力的指标：足底踏步能力直到失败，关节运动形状和运动频率与假手术对照组比较。单独的OEG移植显著增加了横断后7个月进行的足底步数，而单独的训练在任何一个时间点都没有效果。在研究的7个月结束时，只有注射了OEG的大鼠脚底的后爪放置了两步以上。OEG移植结合训练导致每组大鼠足底踏步的比例最高，并且是唯一一组在4个月和7个月的评估期间显著提高其踏步能力的组。此外，OEG移植促进了横断部位的组织保留，促进了横断部位去甲肾上腺素能轴突和5-羟色胺能轴突的再生。有趣的是，注射介质和OEG的大鼠的尾部残端含有类似密度的5-羟色胺能轴突和偶尔5-羟色胺标记的中间神经元。这些数据表明，嗅球来源的OEG移植改善了截瘫大鼠的后肢步态，并进一步表明，特定任务的训练可能会增强这种OEG效应。
Numerous treatment strategies for spinal cord injury seek to maximize recovery of function and two strategies that show substantial promise are olfactory bulb-derived olfactory ensheathing glia (OEG) transplantation and treadmill step training. In this study we re-examined the issue of the effectiveness of OEG implantation but used objective, quantitative measures of motor performance to test if there is a complementary effect of long-term step training and olfactory bulb-derived OEG implantation. We studied complete mid-thoracic spinal cord transected adult female rats and compared four experimental groups: media-untrained, media-trained, OEG-untrained and OEG-trained. To assess the extent of hindlimb locomotor recovery at 4 and 7 months post-transection we used three quantitative measures of stepping ability: plantar stepping performance until failure, joint movement shape and movement frequency compared to sham controls. OEG transplantation alone significantly increased the number of plantar steps performed at 7 months post-transection, while training alone had no effect at either time point. Only OEG-injected rats plantar placed their hindpaws for more than two steps by the 7-month endpoint of the study. OEG transplantation combined with training resulted in the highest percentage of spinal rats per group that plantar stepped, and was the only group to significantly improve its stepping abilities between the 4- and 7-month evaluations. Additionally, OEG transplantation promoted tissue sparing at the transection site, regeneration of noradrenergic axons and serotonergic axons spanning the injury site. Interestingly, the caudal stump of media- and OEG-injected rats contained a similar density of serotonergic axons and occasional serotonin-labelled interneurons. These data demonstrate that olfactory bulb-derived OEG transplantation improves hindlimb stepping in paraplegic rats and further suggest that task-specific training may enhance this OEG effect.