Nogo-A Antibodies and Training Reduce Muscle Spasms in Spinal Cord-Injured Rats
Nogo-A Antibodies and Training Reduce Muscle Spasms in Spinal Cord-Injured Rats
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DOI：
10.1002/ana.22009
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发表时间：
2010-07-01
影响因子：
11.2
通讯作者：
Schwab, Martin E.
中科院分区：
文献类型：
--
作者：
Gonzenbach, Roman R.;Gasser, Pascal;Schwab, Martin E.
目的：脊髓损伤（Spinal cord injury，SCI）是由于上行和下行纤维束的损伤而导致的永久性运动和感觉障碍。此外，在许多患者中发生功能障碍，如神经性疼痛或肌肉痉挛，这可能是由损伤诱导的病变上方和下方神经元回路的可塑性变化引起的。脊髓损伤的新治疗策略旨在增强可塑性和神经突生长，例如，通过阻断关键的神经突生长抑制剂Nogo-A或其下游效应物。因此，至关重要的是调查这种治疗对肌肉痉挛等功能障碍的潜在影响。此外，运动训练，现在是一个标准的治疗工具，以提高步行能力，在不完全SCI的科目，可以预期的影响，重新安排脊髓回路和发展的肌肉痉挛和其他功能障碍。方法和结果：在这里，我们提出并验证了一种新的大鼠模型，用于不完全SCI后的肌肉痉挛，并表明鞘内抗Nogo-A抗体治疗和运动训练，损伤后早期开始，永久性地减少肌肉痉挛的发展。解释：结果表明，抗体介导的生长抑制蛋白Nogo-A的抑制导致功能恢复和较低水平的功能障碍，这表明在受损的脊髓中形成了功能上有意义的连接。SCI后早期的跑步机训练也有有益的效果。神经网络2010;68：48-57
Objective: Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions.Methods and Results: Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms.Interpretation: The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect. ANN NEUROL 2010;68:48-57