Chia Raymond, Zhong Hui, Vissel Bryce, Edgerton V Reggie, Gad Parag
Faculty of Science, Centre for Neuroscience and Regenerative Medicine, University of Technology Sydney, Sydney, NSW, Australia.
St Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.
Front Syst Neurosci. 2020 Jan 15;13:82. doi: 10.3389/fnsys.2019.00082. eCollection 2019.
A mid-thoracic spinal cord injury (SCI) severely impairs activation of the lower limb sensorimotor spinal networks, leading to paralysis. Various neuromodulatory techniques including electrical and pharmacological activation of the spinal networks have been successful in restoring locomotor function after SCI. We hypothesized that the combination of self-training in a natural environment with epidural stimulation (ES), quipazine (Quip), and strychnine (Strych) would result in greater activity in a cage environment after paralysis compared to either intervention alone. To assess this, we developed a method measuring and characterizing the chronic EMG recordings from tibialis anterior (TA) and soleus (Sol) muscles while rats were freely moving in their home cages. We then assessed the relationship between the change in recorded activity over time and motor-evoked potentials (MEPs) in animals receiving treatments. We found that the combination of ES, Quip, and Strych (sqES) generated the greatest level of recovery followed by ES + Quip (qES) while ES + Strych (sES) and ES alone showed least improvement in recorded activity. Further, we observed an exponential relationship between late response (LR) component of the MEPs and spontaneously generated step-like activity. Our data demonstrate the feasibility and potential importance of quantitatively monitoring mechanistic factors linked to activity-dependence in response to combinatorial interventions compared to individual therapies after SCI.
胸段脊髓损伤（SCI）会严重损害下肢感觉运动脊髓网络的激活，导致瘫痪。包括脊髓网络的电刺激和药物激活在内的各种神经调节技术已成功恢复SCI后的运动功能。我们假设，与单独的任何一种干预相比，在自然环境中进行自我训练并结合硬膜外刺激（ES）、喹哌嗪（Quip）和士的宁（Strych），将使瘫痪后的大鼠在笼养环境中表现出更大的活动量。为了评估这一点，我们开发了一种方法，在大鼠在其家笼中自由活动时，测量并表征来自胫骨前肌（TA）和比目鱼肌（Sol）的慢性肌电图记录。然后，我们评估了接受治疗的动物中记录的活动随时间的变化与运动诱发电位（MEP）之间的关系。我们发现，ES、Quip和Strych的组合（sqES）产生的恢复水平最高，其次是ES + Quip（qES），而ES + Strych（sES）和单独的ES在记录的活动中改善最少。此外，我们观察到MEP的迟发反应（LR）成分与自发产生的阶梯状活动之间存在指数关系。我们的数据表明，与SCI后的个体治疗相比，定量监测与组合干预反应中的活动依赖性相关的机制因素具有可行性和潜在重要性。
