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首页> 外文期刊>Molecular brain >Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition
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Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition

机译：通过跑步机训练与semaphorin3A抑制相结合来重新生成轴突

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Background Rats exhibit extremely limited motor function recovery after total transection of the spinal cord (SCT). We previously reported that SM-216289, a semaphorin3A inhibitor, enhanced axon regeneration and motor function recovery in SCT adult rats. However, these effects were limited because most regenerated axons likely do not connect to the right targets. Thus, rebuilding the appropriate connections for regenerated axons may enhance recovery. In this study, we combined semaphorin3A inhibitor treatment with extensive treadmill training to determine whether combined treatment would further enhance the “rewiring” of regenerated axons. In this study, which aimed for clinical applicability, we administered a newly developed, potent semaphorin3A inhibitor, SM-345431 (Vinaxanthone), using a novel drug delivery system that enables continuous drug delivery over the period of the experiment. Results Treatment with SM-345431 using this delivery system enhanced axon regeneration and produced significant, but limited, hindlimb motor function recovery. Although extensive treadmill training combined with SM-345431 administration did not further improve axon regeneration, hindlimb motor performance was restored, as evidenced by the significant improvement in the execution of plantar steps on a treadmill. In contrast, control SCT rats could not execute plantar steps at any point during the experimental period. Further analyses suggested that this strategy reinforced the wiring of central pattern generators in lumbar spinal circuits, which, in turn, led to enhanced motor function recovery (especially in extensor muscles). Conclusions This study highlights the importance of combining treatments that promote axon regeneration with specific and appropriate rehabilitations that promote rewiring for the treatment of spinal cord injury.
机译：背景大鼠脊髓完全横断（SCT）后，其运动功能恢复极为受限。我们以前曾报道过，semaphorin3A抑制剂SM-216289可增强SCT成年大鼠的轴突再生和运动功能恢复。但是，这些作用是有限的，因为大多数再生的轴突可能未连接到正确的靶标。因此，重建用于再生轴突的适当连接可以增强恢复。在这项研究中，我们将semaphorin3A抑制剂治疗与广泛的跑步机训练相结合，以确定联合治疗是否会进一步增强再生轴突的“再生能力”。在这项旨在临床应用的研究中，我们使用了新型药物递送系统，可以在实验期间连续进行药物递送，从而给予了新开发的有效的信号素3A抑制剂SM-345431（Vinaxanthone）。结果使用该递送系统用SM-345431进行的处理增强了轴突再生，并产生了明显但有限的后肢运动功能恢复。尽管大量的跑步机训练与SM-345431的使用相结合并不能进一步改善轴突的再生，但后肢的运动性能得以恢复，这在跑步机上进行足底踩踏可以显着改善。相比之下，在实验期间，对照SCT大鼠在任何时候都无法执行plant骨步骤。进一步的分析表明，该策略加强了腰椎回路中中央模式发生器的布线，进而导致运动功能的恢复增强（尤其是在伸肌中）。结论该研究强调了将促进轴突再生的治疗与促进脊髓重新布线的特异性和适当康复相结合以治疗脊髓损伤的重要性。

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