背景:中风后吞咽困难(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)可以改善中风患者的吞咽功能。然而,很少有研究阐明潜在的分子机制。
方法:采用短暂性大脑中动脉闭塞(tMCAO)建立PSD大鼠模型。将大鼠随机分为假手术组,PSD组,PSD+假rTMS组,PSD+5Hz-rTMS组,PSD+10Hz-rTMS组和PSD+20Hz-rTMS组。将大鼠称重并进行视频透视吞咽研究。肺部炎症,血清P物质(SP)和降钙素基因相关肽(CGRP)水平,肺,和孤束核(NTS),评估NTS中的脑源性神经营养因子(BDNF)和5-羟色胺(5HT)。
结果:PSD组大鼠体重下降,减少推注面积和咽部推注速度,术后第7天和第14天,咽部传输时间(PTT)和吞咽间隔(ISI)增加。此外,PSD大鼠出现肺部炎症,降低肺和血清中的SP水平,肺和NTS中CGRP水平升高,降低NTS中BDNF和5HT的水平。PSD组与PSD+sham-rTMS组的体重和VFSS成果无明显差别。与PSD组相比,丸剂面积显著增加,5HzrTMS干预后大鼠PTT降低。10Hz的HF-rTMS显着增加了重量,bolus面积,咽推注速度和降低大鼠PTT和ISI。推注面积(p<0.01)和咽部推注速度也显着增加,20HzrTMS干预后大鼠PTT和ISI降低。此外,与PSD+5Hz-rTMS组相比,推注面积和咽部推注速度显着增加,PSD+10Hz-rTMS组大鼠吞咽功能ISI降低。此外,与PSD+5Hz-rTMS组相比,PSD+20Hz-rTMS组大鼠吞咽功能ISI显著下降。10Hz的HF-rTMS减轻了肺部炎症,增加了肺中SP的水平,血清,和NTS,血清和NTS中的CGRP,5HT在PSD年夜鼠NTS中的表达。
结论:与5Hz和20HzrTMS相比,10HzrTMS能更有效地改善PSD大鼠的吞咽功能。10Hz的HF-rTMS改善了PSD大鼠的吞咽功能并减轻了肺炎。其机制可能与肺中SP水平升高有关,血清和NTS,血清和NTS中CGRP的水平,5HT在HF-rTMS处置后的NTS。
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.
CONCLUSIONS: 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.