Spinal electro-magnetic stimulation combined with transgene delivery of neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion injury.

Spinal electro-magnetic stimulation combined with transgene delivery of neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion injury.
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脊髓电磁刺激结合神经营养蛋白 NT-3 的转基因递送和运动:脊髓挫伤的新型联合疗法。

DOI:
10.1152/jn.00480.2015
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发表时间:
2015
影响因子:
2.5
通讯作者:
V. Arvanian
V. Arvanian
中科院分区:
医学3区
文献类型:
--
作者:
Hayk A. Petrosyan;Valentina Alessi;Arsen Hunanyan;S. Sisto;V. Arvanian

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我们最近的终端实验显示,单次重复性脊髓电磁刺激(sEMS; 35分钟)可增强脊髓半切外侧损伤后脊髓回路的突触可塑性。在目前的研究中,我们研究了胸腔T10挫伤后重复sEMS作为单一训练和长期(5周,每隔一天)的效果。慢性研究包括检查系统sEMS单独给药和联合运动训练和转基因传递神经营养因子[腺相关病毒10-神经营养因子3 (AAV10-NT3)]。通过电生理细胞内/细胞外记录、免疫组织化学、行为测试和解剖追踪来评估治疗效果。我们发现,在慢性挫伤大鼠中,单次sEMS训练可诱导通过保存的外侧白质到运动神经元和后肢肌肉的瞬时促进传递,其影响持续至少2小时。这些生理变化与腰神经元中GluR1和GluR2/3谷氨酸受体的免疫反应性增加有关。然而,系统地单独给予sEMS 5周,不能诱导脊髓肌肉回路的累积改善或改善胸挫伤后受损的运动功能。令人鼓舞的是,长期给予sEMS,然后进行运动训练(在健身球中跑步和游泳),诱导以下情况:1)持续加强腰椎运动神经元和后肢肌肉的传递,2)更好的逆行运输解剖示踪剂,3)改善运动功能。在接受运动结合sEMS和AAV-NT3的组中,观察到最大的改善。
Our recent terminal experiments revealed that administration of a single train of repetitive spinal electromagnetic stimulation (sEMS; 35 min) enhanced synaptic plasticity in spinal circuitry following lateral hemisection spinal cord injury. In the current study, we have examined effects of repetitive sEMS applied as a single train and chronically (5 wk, every other day) following thoracic T10 contusion. Chronic studies involved examination of systematic sEMS administration alone and combined with exercise training and transgene delivery of neurotrophin [adeno-associated virus 10-neurotrophin 3 (AAV10-NT3)]. Electrophysiological intracellular/extracellular recordings, immunohistochemistry, behavioral testing, and anatomical tracing were performed to assess effects of treatments. We found that administration of a single sEMS train induced transient facilitation of transmission through preserved lateral white matter to motoneurons and hindlimb muscles in chronically contused rats with effects lasting for at least 2 h. These physiological changes associated with increased immunoreactivity of GluR1 and GluR2/3 glutamate receptors in lumbar neurons. Systematic administration of sEMS alone for 5 wk, however, was unable to induce cumulative improvements of transmission in spinomuscular circuitry or improve impaired motor function following thoracic contusion. Encouragingly, chronic administration of sEMS, followed by exercise training (running in an exercise ball and swimming), induced the following: 1) sustained strengthening of transmission to lumbar motoneurons and hindlimb muscles, 2) better retrograde transport of anatomical tracer, and 3) improved locomotor function. Greatest improvements were seen in the group that received exercise combined with sEMS and AAV-NT3.
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发表时间: 1999-01-01
影响因子: 2.5
作者:
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