A new measure of cortical inhibition by mechanomyography and paired-pulse transcranial magnetic stimulation in unanesthetized rats
A new measure of cortical inhibition by mechanomyography and paired-pulse transcranial magnetic stimulation in unanesthetized rats
复制标题
DOI：
10.1152/jn.00690.2011
复制
发表时间：
2012-02-01
影响因子：
2.5
通讯作者：
Rotenberg, Alexander
中科院分区：
文献类型：
--
作者：
Hsieh, Tsung-Hsun;Dhamne, Sameer C.;Rotenberg, Alexander
谢天华，Dhamne SC，Chen J-J，Pascual-Leone A，Jensen FE，Rotenberg A。机械肌图和双脉冲经颅磁刺激对非麻醉大鼠皮质抑制的新方法。神经生理学杂志107：966-972,2012。2011年10月19日首次出版；DOI：10.1152/jn.00690.2011。-成对脉冲经颅磁刺激(PpTMS)是一种安全和非侵入性的工具，用于测量人类的皮质抑制，特别是在患有皮质抑制障碍的患者，如癫痫。然而，在啮齿动物疾病模型中，ppTMS方案由于对麻醉和针状肌电图的要求而受到限制，在这种模型中，可以获得对ppTMS生理和疾病过程的机械性洞察。为了消除麻醉的混杂因素，使清醒大鼠的ppTMS反应更接近于人，我们采用机械肌图(MMG)方法研究清醒大鼠的ppTMS抑制现象，并应用差异药理学方法验证长间期皮质抑制是由GABA(A)受体介导的假说。以50、100和200ms为间隔的长间隔ppTMS方案，在清醒大鼠中诱发双侧后肢诱发的MMG。分别于注射生理盐水、GABA(A)激动剂戊巴比妥(PB)和GABA(A)拮抗剂戊四唑(PTZ)前、后测定ppTMS-MMG的急性变化。单次脉冲刺激可使100%的动物获得诱发的MMG，ppTMS可预测地抑制测试诱发的MMG。随着TMS强度的增加，MMG幅度与机器输出成比例增加，以产生可靠的输入-输出曲线。肌电和MMG同步记录显示运动诱发电位和诱发MMG之间的潜伏期存在可预测的差异(分别为7.55±0.08和9.16±0.14 ms)。通过药理实验，时程观察显示，注射PTZ后，ppTMS-MMG的抑制作用显著降低(P&t；0.05)，PB注射后，ppTMS-MMG的抑制作用显著增强，1h后恢复到治疗前水平。我们的数据支持应用ppTMS-MMG技术测量清醒大鼠的皮层兴奋性，并为GABA(A)受体参与长间隔双脉冲皮质抑制提供了证据。因此，ppTMS-MMG是一种耐受性良好的生物标志物，可用于测量GABA(A)介导的大鼠皮质抑制。
Hsieh T-H, Dhamne SC, Chen J-J, Pascual-Leone A, Jensen FE, Rotenberg A. A new measure of cortical inhibition by mechanomyography and paired-pulse transcranial magnetic stimulation in unanesthetized rats. J Neurophysiol 107: 966-972, 2012. First published October 19, 2011; doi:10.1152/jn.00690.2011.-Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive tool for measuring cortical inhibition in humans, particularly in patients with disorders of cortical inhibition such as epilepsy. However, ppTMS protocols in rodent disease models, where mechanistic insight into the ppTMS physiology and into disease processes may be obtained, have been limited due to the requirement for anesthesia and needle electromyography. To eliminate the confounding factor of anesthesia and to approximate human ppTMS protocols in awake rats, we adapted the mechanomyogram (MMG) method to investigate the ppTMS inhibitory phenomenon in awake rats and then applied differential pharmacology to test the hypothesis that long-interval cortical inhibition is mediated by the GABA(A) receptor. Bilateral hindlimb-evoked MMGs were elicited in awake rats by long-interval ppTMS protocols with 50-, 100-, and 200-ms interstimulus intervals. Acute changes in ppTMS-MMG were measured before and after intraperitoneal injections of saline, the GABA(A) agonist pentobarbital (PB), and GABA(A) antagonist pentylenetetrazole (PTZ). An evoked MMG was obtained in 100% of animals by single-pulse stimulation, and ppTMS resulted in predictable inhibition of the test-evoked MMG. With increasing TMS intensity, MMG amplitudes increased in proportion to machine output to produce reliable input-output curves. Simultaneous recordings of electromyography and MMG showed a predictable latency discrepancy between the motor-evoked potential and the evoked MMG (7.55 +/- 0.08 and 9.16 +/- 0.14 ms, respectively). With pharmacological testing, time course observations showed that ppTMS-MMG inhibition was acutely reduced following PTZ (P < 0.05), acutely enhanced after PB (P < 0.01) injection, and then recovered to pretreatment baseline after 1 h. Our data support the application of the ppTMS-MMG technique for measuring the cortical excitability in awake rats and provide the evidence that GABA(A) receptor contributes to long-interval paired-pulse cortical inhibition. Thus ppTMS-MMG appears a well-tolerated biomarker for measuring GABA (A)-mediated cortical inhibition in rats.