Cervical spinal cord injury (CSCI) can induce lifelong disabilities, including spasticity and gait impairments. The objective of this pre-clinical study was to evaluate the therapeutic effects of simultaneous and combined early locomotor treadmill training (Tm) and injury site magnetic stimulation (TMSsc) on spasticity and gait impairments in a rat model of C_6/7 moderate contusion SCI. The Tm training was initiated at post-injury (PI) day 8, whereas TMS treatment was added to Tm 14 days PI, and then the combined therapy (TMSTm) was continued for six weeks. Untreated CSCI animals revealed significant and enduring hindlimb spasticity (measured as velocity-dependent ankle torques and time-locked triceps surae electromyography), significant alterations in limb coordination, and significant reductions in forelimb grip strength. The TMSTm showed significantly lower spasticity, significantly more normal limb coordination (quantitated using three-dimensional (3D) kinematics and Catwalk gait analyses), and significantly greater forelimb grip strength compared with the CSCI untreated controls. In addition, three-dimensional gradient echo and diffusion tensor magnetic resonance imaging showed that TMSTm treated animals had smaller cavity volumes and better preservation of the white matter. In addition, compared with the CSCI untreated animals, the lumbar spinal cord (SC) of the treatment group revealed significant up-regulation of dopamine beta-hydroxylase, glutamic acid decarboxylase, gamma-aminobutyric acid receptor B, and brain-derived neurotrophic factor. The treatment-induced up-regulation of these molecules may have enhanced the activity-induced adaptive plasticity in the SC and contributed to normalization of pre- and post-synaptic reflex regulatory processes. In addition, the TMSTm therapy may have decreased injury-induced progressive maladaptive segmental and descending plasticity. Our data are the first to suggest that an early simultaneous combination of Tm and injury-site TMSsc application can be an effective therapy for CSCI-induced spasticity and gait impairments. These pre-clinical data demonstrated the feasibility and efficacy of a novel therapeutic strategy for SCI-induced spasticity and gait impairments.

中文翻译：

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同时结合跑步机训练和磁刺激对颈脊髓损伤后痉挛和步态障碍的影响。

颈脊髓损伤 (CSCI) 可导致终身残疾，包括痉挛和步态障碍。这项临床前研究的目的是评估同时和联合早期运动跑步机训练 (Tm) 和损伤部位磁刺激 (TMSsc) 对 C _6/7大鼠模型痉挛和步态障碍的治疗效果中度挫伤 SCI。Tm 训练在伤后 (PI) 第 8 天开始，而 TMS 治疗添加到 Tm PI 14 天，然后联合治疗 (TMSTm) 持续六周。未经治疗的 CSCI 动物显示出显着且持久的后肢痉挛（测量为速度依赖的踝关节扭矩和时间锁定的小腿三头肌肌电图）、肢体协调的显着改变和前肢握力的显着降低。与未治疗的 CSCI 对照组相比，TMSTm 显示出显着较低的痉挛状态，显着更正常的肢体协调（使用三维 (3D) 运动学和猫步步态分析进行量化），以及显着更大的前肢握力。此外，三维梯度回波和弥散张量磁共振成像显示，TMSTm 治疗的动物腔体积更小，白质保存更好。此外，与未治疗的 CSCI 动物相比，治疗组的腰脊髓 (SC) 显示多巴胺 β-羟化酶、谷氨酸脱羧酶、γ-氨基丁酸受体 B 和脑源性神经营养因子的显着上调。这些分子的治疗诱导上调可能增强了 SC 中活动诱导的适应性可塑性，并有助于突触前和突触后反射调节过程的正常化。此外，TMSTm 治疗可能降低了损伤引起的进行性适应不良节段性和下行可塑性。我们的数据首次表明 Tm 和损伤部位 TMSsc 应用的早期同时组合可以成为治疗 CSCI 引起的痉挛和步态障碍的有效疗法。这些临床前数据证明了一种针对 SCI 引起的痉挛和步态障碍的新型治疗策略的可行性和有效性。