Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-a
Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-a
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DOI：
10.1523/jneurosci.21-10-03665.2001
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发表时间：
2001-05-15
影响因子：
5.3
通讯作者：
Fouad, K
中科院分区：
文献类型：
--
作者：
Merkler, D;Metz, GAS;Fouad, K
成年哺乳动物CNS中轴突有限的可塑性和再生能力可通过应用抗髓鞘相关神经突生长抑制剂Nogo-A的单克隆抗体（mAb）IN- 1来增强。本研究的目的是探讨这种治疗对脊髓背侧过半横断成年大鼠功能恢复的影响。损伤后，立即将一半的动物植入分泌mAb IN- 1的杂交瘤细胞，而其他动物则接受分泌对照抗体（抗HRP）的细胞。广泛的运动测试（旷场运动）评分、网格行走、失步退缩反应、窄梁交叉）用于表征损伤后5周期间的运动恢复。在所有行为测试中，与对照抗体处理的大鼠相比，mAb IN- 1处理组的恢复显著增强。在跑步机行走期间屈肌和伸肌的EMG记录证实了mAb IN- 1处理的大鼠中运动模式的改善;步循环持续时间、节律性和后肢的耦合显著改善。在术后5周的甩尾试验中，两组之间的伤害性感受没有差异。这些表明功能恢复改善的结果表明，Nogo-A中和后CNS的可塑性和再生能力增加导致运动系统功能上有意义的重新布线。
The limited plastic and regenerative capabilities of axons in the adult mammalian CNS can be enhanced by the application of a monoclonal antibody (mAb), IN- 1, raised against the myelin-associated neurite growth inhibitor Nogo- A. The aim of the present study was to investigate the effects of this treatment on the functional recovery of adult rats with a dorsal overhemisection of the spinal cord. Directly after injury, half of the animals were implanted with mAb IN- 1- secreting hybridoma cells, whereas the others received cells secreting a control antibody (anti- HRP). A broad spectrum of locomotor tests (open field locomotor) score, grid walk, misstep withdrawal response, narrow- beam crossing) was used to characterize locomotor recovery during the 5 weeks after the injury. In all behavioral tests, the recovery in the mAb IN- 1- treated group was significantly augmented compared with the control antibody-treated rats. EMG recordings of flexor and extensor muscles during treadmill walking confirmed the improvement of the locomotor pattern in the mAb IN- 1- treated rats; step- cycle duration, rhythmicity, and coupling of the hindlimbs were significantly improved. No differences between the two groups with regard to nociception were observed in the tail flick test 5 weeks after the operation. These results indicating improved functional recovery suggest that the increased plastic and regenerative capabilities of the CNS after Nogo- A neutralization result in a functionally meaningful rewiring of the motor systems.