Long Lu, Zang Qianwen, Jia Gongwei, Fan Meng, Zhang Liping, Qi Yingqiang, Liu Yilin, Yu Lehua, Wang Sanrong
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Traditional Chinese Medicine, Weinan Central Hospital, Weinan, China.
Front Behav Neurosci. 2022 Apr 4;16:811419. doi: 10.3389/fnbeh.2022.811419. eCollection 2022.
Clinical and animal studies have shown that transcutaneous auricular vagus nerve stimulation (ta-VNS) exerts neuroprotection following cerebral ischemia. Studies have revealed that white matter damage after ischemia is related to swallowing defects, and the degree of white matter damage is related to the severity of dysphagia. However, the effect of ta-VNS on dysphagia symptoms and white matter damage in dysphagic animals after an ischemic stroke has not been investigated.
Middle cerebral artery occlusion (MCAO) rats were randomly divided into the sham, control and vagus nerve stimulation (VNS) group, which subsequently received ta-VNS for 3 weeks. The swallowing reflex was measured once weekly by electromyography (EMG). White matter remyelination, volume, angiogenesis and the inflammatory response in the white matter were assessed by electron microscopy, immunohistochemistry, stereology, enzyme-linked immunosorbent assay (ELISA) and Western blotting.
ta-VNS significantly increased the number of swallows within 20 s and reduced the onset latency to the first swallow. ta-VNS significantly improved remyelination but did not alleviate white matter shrinkage after MCAO. Stereology revealed that ta-VNS significantly increased the density of capillaries and increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) expression in the white matter. ta-VNS significantly alleviated the increase inTLR4, MyD88, phosphorylated MAPK and NF-κB protein levels and suppressed the expression of the proinflammatory factors IL-1β and TNF-α.
These results indicated ta-VNS slightly improved dysphagia symptoms after ischemic stroke, possibly by increasing remyelination, inducing angiogenesis, and inhibiting the inflammatory response in the white matter of cerebral ischaemia model rats, implying that ta-VNS may be an effective therapeutic strategy for the treatment of dysphagia after ischemic stroke.
临床和动物研究表明，经皮耳迷走神经刺激（ta-VNS）在脑缺血后发挥神经保护作用。研究显示，缺血后的白质损伤与吞咽缺陷有关，且白质损伤程度与吞咽困难的严重程度相关。然而，尚未研究ta-VNS对缺血性卒中后吞咽困难动物的吞咽困难症状和白质损伤的影响。
将大脑中动脉闭塞（MCAO）大鼠随机分为假手术组、对照组和迷走神经刺激（VNS）组，随后对VNS组大鼠进行3周的ta-VNS治疗。每周通过肌电图（EMG）测量一次吞咽反射。通过电子显微镜、免疫组织化学、体视学、酶联免疫吸附测定（ELISA）和蛋白质印迹法评估白质的再髓鞘化、体积、血管生成和白质中的炎症反应。
ta-VNS显著增加了20秒内的吞咽次数，并缩短了首次吞咽的起始潜伏期。ta-VNS显著改善了再髓鞘化，但并未减轻MCAO后的白质萎缩。体视学显示，ta-VNS显著增加了毛细血管密度，并增加了白质中血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（FGF2）的表达。ta-VNS显著减轻了TLR4、MyD88、磷酸化MAPK和NF-κB蛋白水平的升高，并抑制了促炎因子IL-1β和TNF-α的表达。
这些结果表明，ta-VNS可能通过增加再髓鞘化、诱导血管生成和抑制脑缺血模型大鼠白质中的炎症反应，略微改善缺血性卒中后的吞咽困难症状，这意味着ta-VNS可能是治疗缺血性卒中后吞咽困难的有效治疗策略。
