Gonzalez-Rothi Elisa J, Streeter Kristi A, Hanna Marie H, Stamas Anna C, Reier Paul J, Baekey David M, Fuller David D
McKnight Brain Institute, Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida;
McKnight Brain Institute, Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida.
J Neurophysiol. 2017 Oct 1;118(4):2344-2357. doi: 10.1152/jn.00913.2016. Epub 2017 Jun 14.
C2 spinal hemilesion (C2Hx) paralyzes the ipsilateral diaphragm, but recovery is possible through activation of "crossed spinal" synaptic inputs to ipsilateral phrenic motoneurons. We tested the hypothesis that high-frequency epidural stimulation (HF-ES) would potentiate ipsilateral phrenic output after subacute and chronic C2Hx. HF-ES (300 Hz) was applied to the ventrolateral C4 or T2 spinal cord ipsilateral to C2Hx in anesthetized and mechanically ventilated adult rats. Stimulus duration was 60 s, and currents ranged from 100 to 1,000 µA. Bilateral phrenic nerve activity and ipsilateral hypoglossal (XII) nerve activity were recorded before and after HF-ES. Higher T2 stimulus currents potentiated ipsilateral phasic inspiratory activity at both 2 and 12 wk post-C2Hx, whereas higher stimulus currents delivered at C4 potentiated ipsilateral phasic phrenic activity only at 12 wk ( = 0.028). Meanwhile, tonic output in the ipsilateral phrenic nerve reached 500% of baseline values at the high currents with no difference between 2 and 12 wk. HF-ES did not trigger inspiratory burst-frequency changes. Similar responses occurred following T2 HF-ES. Increases in contralateral phrenic and XII nerve output were induced by C4 and T2 HF-ES at higher currents, but the relative magnitude of these changes was small compared with the ipsilateral phrenic response. We conclude that following incomplete cervical spinal cord injury, HF-ES of the ventrolateral midcervical or thoracic spinal cord can potentiate efferent phrenic motor output with little impact on inspiratory burst frequency. However, the substantial increases in tonic output indicate that the uninterrupted 60-s stimulation paradigm used is unlikely to be useful for respiratory muscle activation after spinal injury. Previous studies reported that high-frequency epidural stimulation (HF-ES) activates the diaphragm following acute spinal transection. This study examined HF-ES and phrenic motor output following subacute and chronic incomplete cervical spinal cord injury. Short-term potentiation of phrenic bursting following HF-ES illustrates the potential for spinal stimulation to induce respiratory neuroplasticity. Increased tonic phrenic output indicates that alternatives to the continuous stimulation paradigm used in this study will be required for respiratory muscle activation after spinal cord injury.
C2脊髓半横断损伤（C2Hx）会导致同侧膈肌麻痹，但通过激活对同侧膈运动神经元的“交叉脊髓”突触输入，恢复是有可能的。我们检验了这样一个假设：高频硬膜外刺激（HF-ES）会在亚急性和慢性C2Hx后增强同侧膈神经输出。在麻醉并机械通气的成年大鼠中，将HF-ES（300赫兹）施加于C2Hx同侧的C4或T2脊髓腹外侧。刺激持续时间为60秒，电流范围为100至1000微安。在HF-ES前后记录双侧膈神经活动和同侧舌下（XII）神经活动。较高的T2刺激电流在C2Hx后2周和12周时均增强了同侧的阶段性吸气活动，而在C4施加的较高刺激电流仅在12周时增强了同侧的阶段性膈神经活动（P = 0.028）。同时，在高电流下，同侧膈神经的紧张性输出达到基线值的500%，2周和12周之间无差异。HF-ES未引发吸气爆发频率变化。T2 HF-ES后出现类似反应。在较高电流下，C4和T2 HF-ES诱导了对侧膈神经和XII神经输出增加，但与同侧膈神经反应相比，这些变化的相对幅度较小。我们得出结论，在不完全颈脊髓损伤后，颈中或胸段脊髓腹外侧的HF-ES可增强膈运动传出输出，对吸气爆发频率影响很小。然而，紧张性输出的大幅增加表明，所使用的60秒不间断刺激模式不太可能对脊髓损伤后的呼吸肌激活有用。先前的研究报告称，高频硬膜外刺激（HF-ES）在急性脊髓横断后可激活膈肌。本研究检查了亚急性和慢性不完全颈脊髓损伤后的HF-ES和膈运动输出。HF-ES后膈神经爆发的短期增强说明了脊髓刺激诱导呼吸神经可塑性的潜力。紧张性膈神经输出增加表明，脊髓损伤后呼吸肌激活需要本研究中使用的连续刺激模式的替代方法。
