Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China.
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China; Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Traditional Chinese Medicine, 232 East Waihuan Road, Guangzhou 510006, Guangdong Province, China.
Brain Res. 2024 Jun 1;1832:148846. doi: 10.1016/j.brainres.2024.148846. Epub 2024 Mar 1.
BACKGROUND: Post-stroke dysphagia (PSD) is a common symptom of stroke. Clinical complications of PSD include malnutrition and pneumonia. Clinical studies have shown that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) can improve the swallowing function in stroke patients. However, few studies have elucidated the underlying molecular mechanisms. METHODS: A PSD rat model was established using transient middle cerebral artery occlusion (tMCAO). Rats were randomly divided into sham-operated groups, PSD groups, PSD + sham-rTMS groups, PSD + 5 Hz-rTMS groups, PSD + 10 Hz-rTMS groups and PSD + 20 Hz-rTMS groups. Rats were weighed and videofluoroscopic swallowing studies were conducted. Pulmonary inflammation, levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in the serum, lung, and nucleus tractus solitarius (NTS), brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5HT) in NTS were evaluated. RESULTS: Rats in the PSD group experienced weight loss, reduced bolus area and pharyngeal bolus speed, and increased pharyngeal transit time (PTT) and inter-swallow interval (ISI) on day 7 and day 14 after operation. Moreover, PSD rats showed pulmonary inflammation, reduced levels of SP in the lung and serum, increased levels of CGRP in the lung and NTS, reduced levels of BDNF and 5HT in the NTS. There was no significant difference between the PSD group and the PSD + sham-rTMS group in the results of weight and VFSS. Comparing with the PSD group, there significant increases in the bolus area, decreases in PTT of rats following 5 Hz rTMS intervention. HF-rTMS at 10 Hz significantly increased the weight, bolus area, pharyngeal bolus speed and decreased the PTT and ISI of rats. There were also significant increases in the bolus area (p < 0.01) and pharyngeal bolus speed, decreases in PTT and ISI of rats following 20 Hz rTMS intervention. Furthermore, compared with the PSD + 5 Hz-rTMS group, there were significant increases in the bolus area and pharyngeal bolus speed, decreases in ISI in the swallowing function of rats in the PSD + 10 Hz-rTMS group. Besides, compared with the PSD + 5 Hz-rTMS group, there were significant decreases in ISI in the swallowing function of rats in the PSD + 20 Hz-rTMS group. HF-rTMS at 10 Hz alleviated pulmonary inflammation, increased the levels of SP in the lung, serum, and NTS, CGRP in the serum and NTS, 5HT in the NTS of PSD rats. CONCLUSION: Compared with 5 Hz and 20 Hz rTMS, 10 Hz rTMS more effectively improved the swallowing function of rats with PSD. HF-rTMS at 10 Hz improved the swallowing function and alleviated pneumonia in PSD rats. The mechanism may be related to increased levels of SP in the lung, serum and NTS, levels of CGRP in the serum and NTS, 5HT in the NTS after HF-rTMS treatment.
背景：卒中后吞咽困难（PSD）是中风的常见症状。 PSD 的临床并发症包括营养不良和肺炎。临床研究表明，高频重复经颅磁刺激（HF-rTMS）可改善中风患者的吞咽功能。然而，很少有研究阐明其潜在的分子机制。
方法：采用短暂性大脑中动脉闭塞（tMCAO）建立 PSD 大鼠模型。大鼠随机分为假手术组、 PSD 组、 PSD+假 rTMS 组、 PSD+5 Hz-rTMS 组、 PSD+10 Hz-rTMS 组和 PSD+20 Hz-rTMS 组。称重并进行视频荧光透视吞咽研究。评估肺炎症、血清、肺和孤束核（NTS）中 P 物质（SP）和降钙素基因相关肽（CGRP）水平、脑源性神经营养因子（BDNF）和 NTS 中的 5-羟色胺（5HT）。
结果： PSD 组大鼠术后第 7 天及第 14 天出现体重减轻、食团面积减小、咽部食团速度减慢、咽部通过时间（PTT）和吞咽间隔时间（ISI）延长。此外， PSD 大鼠肺组织炎症明显，肺和血清中 SP 水平降低，肺和 NTS 中 CGRP 水平升高，NTS 中 BDNF 和 5HT 水平降低。 PSD 组和 PSD+假 rTMS 组在体重和 VFSS 结果方面无显著差异。与 PSD 组相比，5 Hz rTMS 干预后大鼠的食团面积增加，PTT 缩短。 HF-rTMS 频率为 10 Hz 时，大鼠体重、食团面积、咽部食团速度增加，PTT 和 ISI 缩短。与 PSD+5 Hz-rTMS 组相比，20 Hz rTMS 干预后大鼠的食团面积和咽部食团速度增加，ISI 缩短。此外，与 PSD+5 Hz-rTMS 组相比， PSD+10 Hz-rTMS 组大鼠的吞咽功能中食团面积和咽部食团速度增加，ISI 缩短。此外，与 PSD+5 Hz-rTMS 组相比， PSD+20 Hz-rTMS 组大鼠的吞咽功能中 ISI 缩短。 10 Hz HF-rTMS 可减轻肺组织炎症，增加 PSD 大鼠肺、血清和 NTS 中 SP 水平，血清和 NTS 中 CGRP 水平，NTS 中 5HT 水平。
结论：与 5 Hz 和 20 Hz rTMS 相比，10 Hz rTMS 更有效地改善 PSD 大鼠的吞咽功能。 10 Hz HF-rTMS 改善 PSD 大鼠的吞咽功能并减轻肺炎。其机制可能与 HF-rTMS 治疗后肺、血清和 NTS 中 SP 水平升高、血清和 NTS 中 CGRP 水平升高、NTS 中 5HT 水平升高有关。
Brain Stimul. 2016-8-11
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