Alam Monzurul, Garcia-Alias Guillermo, Jin Benita, Keyes Jonathan, Zhong Hui, Roy Roland R, Gerasimenko Yury, Lu Daniel C, Edgerton V Reggie
Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States.
Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, United States; Brain Research Institute, University of California, Los Angeles, CA 90095, United States.
Exp Neurol. 2017 May;291:141-150. doi: 10.1016/j.expneurol.2017.02.006. Epub 2017 Feb 10.
Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6- C8+ and C6+ C8-) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6- Ref+ and C8- Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.
通过脊髓硬膜外电刺激实现运动控制是脊髓损伤（SCI）后运动功能恢复的一种有前景的治疗技术。尽管硬膜外电刺激已使后肢运动功能得到改善，但对于改善颈髓损伤后的前肢精细运动功能是否具有治疗益处尚不清楚。我们测试了在大鼠颈髓损伤后，在脊髓C6和C8节段施加脉冲串是否会促进前肢精细运动控制的恢复。训练大鼠去够取并抓取糖丸。在C4水平进行背侧索挤压损伤后，大鼠在前肢精细运动控制方面立即出现明显缺陷。在损伤后10周，对大鼠在有无颈段硬膜外刺激的情况下进行够取和抓取测试。为了确定激活参与前肢运动功能的颈髓网络的最佳刺激参数，在进行够取和抓取任务的同时，以不同频率（20、40和60Hz）施加单极和双极电流。我们发现，与无刺激条件相比，颈段硬膜外刺激提高了够取和抓取成功率。双极刺激（C6 - C8 +和C6 + C8 -）产生的脊髓运动诱发电位（sMEP）最大，与单极刺激（C6 - Ref +和C8 - Ref +）相比，导致更高的够取和抓取成功率。在20、40和60Hz的刺激频率下进行测试时，前肢表现相似。我们还发现，大多数前肢肌肉的肌电图活动以及屈肌和伸肌之间的共同激活在损伤后增加。然而，在硬膜外刺激下，这种趋势发生了逆转，表明颈段硬膜外脊髓刺激对颈髓损伤后的康复具有治疗潜力。
