High frequency repetitive Transcranial Magnetic Stimulation promotes long lasting phrenic motoneuron excitability via GABAergic networks.

High frequency repetitive Transcranial Magnetic Stimulation promotes long lasting phrenic motoneuron excitability via GABAergic networks.
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DOI:
10.1016/j.resp.2021.103704
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发表时间:
2021-10
影响因子:
2.3
通讯作者:
Vinit, Stephane
Vinit, Stephane
中科院分区:
医学4区
文献类型:
--
作者:
Michel-Flutot, Pauline;V. Zholudeva, Lyandysha;Randelman, Margo L.;Deramaudt, Therese B.;Mansart, Arnaud;Alvarez, Jean-Claude;Lee, Kun-Ze;Petitjean, Michel;Bonay, Marcel;Lane, Michael A.;Vinit, Stephane

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重复经颅磁刺激(rTMS)是一种有前景的、创新的、无创的临床治疗方法。rTMS已被证明可以通过调节受影响的神经回路来改善精神疾病和神经性疼痛。然而,关于rTMS促进这些功能作用的机制和特定的神经回路知之甚少。这项研究的目的是开始揭示rTMS可能利用现有神经回路的机制,通过使用一个很好的脊髓运动回路-膈回路。本研究假设rTMS可以增强麻醉大鼠膈运动神经元的兴奋性。使用多种急性rTMS方案显示,10hz rTMS方案诱导膈运动神经元兴奋性强劲、持久的增加,通过隔膜运动诱发电位进行功能评估(与基线相比,10hz方案60分钟后增加59.1±21.1%,而时间控制方案为6.0±5.8% (p = 0.007), 3hz方案为- 5.8±7.4% (p < 0.001), 30hz方案为5.2±12.5% (p = 0.008))。更深入的分析允许在10赫兹rTMS治疗的动物中区分“反应者”和“无反应者”亚组。在10hz rTMS治疗前静脉注射GABAA和GABAB受体激动剂,可消除增强的膈运动神经元兴奋性,提示gaba能输入在rTMS诱导的膈兴奋性中起机制作用。这些数据表明,10hz的单一高频rTMS方案增加了膈运动神经元的兴奋性,这是由局部gaba能“去抑制”介导的。通过了解rTMS如何用于非侵入性影响神经回路,我们可以开始利用这种神经调节策略的治疗潜力来促进中枢神经系统疾病或损伤后的恢复。
Repetitive transcranial magnetic stimulation (rTMS) is a promising, innovative, and non-invasive therapy used clinically. Efficacy of rTMS has been demonstrated to ameliorate psychiatric disorders and neuropathic pain through neuromodulation of affected neural circuits. However, little is known about the mechanisms and the specific neural circuits via which rTMS facilitates these functional effects. The aim of this study was to begin revealing the mechanisms by which rTMS may tap into existing neural circuits, by using a well characterized spinal motor circuit – the phrenic circuit. Here we hypothesized that rTMS can be used to enhance phrenic motoneuron excitability in anesthetized Sprague Dawley rats. Multiple acute rTMS protocols were used revealing 10 Hz rTMS protocol induced a robust, long-lasting increase in phrenic motoneuron excitability, functionally evaluated by diaphragm motor evoked potentials (59.1 ± 21.1 % of increase compared to baseline 60 min after 10 Hz protocol against 6.0 ± 5.8 % (p = 0.007) for Time Control, −5.8 ± 7.4 % (p < 0.001) for 3 Hz, and 5.2 ± 12.5 % (p = 0.008) for 30 Hz protocols). A deeper analyze allowed to discriminate “responder” and “non-responder” subgroups among 10 Hz rTMS treated animals. Intravenous injections of GABAA and GABAB receptor agonists prior to 10 Hz rTMS treatment, abolished the enhanced phrenic motoneuron excitability, suggesting GABAergic input plays a mechanistic role in rTMS-induced phrenic excitability. These data demonstrate that a single high frequency rTMS protocol at 10 Hz increases phrenic motoneuron excitability, mediated by a local GABAergic “disinhibition”. By understanding how rTMS can be used to affect neural circuits non-invasively we can begin to harness the therapeutic potential of this neuromodulatory strategy to promote recovery after disease or injury to the central nervous system.
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