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针刺通过 KCC2 介导的脊髓 GABA 激活缓解缺血性脑卒中后痉挛性高张力大鼠的脊髓过度反射和运动功能障碍。

Acupuncture alleviates spinal hyperreflexia and motor dysfunction in post-ischemic stroke rats with spastic hypertonia via KCC2-mediated spinal GABA activation.

机构信息

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China; The Key Unit of State Administration of Traditional Chinese Medicine, Evaluation of Characteristic Acupuncture Therapy, Beijing 100029, China.

出版信息

Exp Neurol. 2022 Aug;354:114027. doi: 10.1016/j.expneurol.2022.114027. Epub 2022 Mar 2.

Abstract

The majority of patients simultaneously develop motor dysfunction and spastic hypertonia after ischemic strokes, which can be associated with an increasing trend in motor impairments, seriously impeding the rehabilitation process. Evidence suggests that some deficits in the KCC2 expression in the spinal cord along with maladaptive endogenous plasticity via GABA receptors are often involved in the pathology of spastic hypertonia after a stroke. In this respect, acupuncture has been commonly used in clinical settings for post-stroke patients' rehabilitation. Nevertheless, the mechanism of the modulating activity of this alternative medicine in the spinal pathways to relieve spasticity and improve functional recovery after a stroke has still remained unclear. Utilizing laser speckle imaging, functional assessments (viz. neurologic function scale, muscular tension scale, foot balance test, and gait analysis), H-reflex recording, TTC, Western blotting, RT-qPCR, ELISA, and immunofluorescence molecular assay, the study results illustrated that acupuncture could significantly alleviate the spinal hyperreflexia, decrease muscle tone, and enhance locomotor function by elevating the GABA, KCC2, and GABA expressions in the lumbar spine of a rat model of post-ischemic stroke with spastic hypertonia. Furthermore, the KCC2 antagonist DIOA abolished the benefits induced by this practice. Overall, the data revealed that acupuncture is a promising therapeutic approach for spastic hypertonia after a stroke, and the positive outcomes in this sense could be achieved via activating the KCC2-mediated spinal GABA signaling pathway.

摘要

大多数缺血性中风患者同时出现运动功能障碍和痉挛性肌强直,这可能与运动损伤的增加趋势有关,严重阻碍康复过程。有证据表明,脊髓中 KCC2 表达的一些缺陷以及 GABA 受体的适应性内源性可塑性通常与中风后痉挛性肌强直的病理有关。在这方面,针灸已在临床环境中广泛用于中风患者的康复。然而,这种替代医学在脊髓途径中调节活动以减轻痉挛和改善中风后功能恢复的机制仍不清楚。利用激光散斑成像、功能评估(即神经功能量表、肌肉张力量表、足部平衡测试和步态分析)、H 反射记录、TTC、Western blot、RT-qPCR、ELISA 和免疫荧光分子分析,研究结果表明,针灸可以通过提高缺血性中风后痉挛性肌强直大鼠模型腰椎中的 GABA、KCC2 和 GABA 表达,显著减轻脊髓反射亢进、降低肌肉张力和增强运动功能。此外,KCC2 拮抗剂 DIOA 消除了这种做法带来的益处。总的来说,数据表明,针灸是一种有前途的治疗中风后痉挛性肌强直的方法,从这个意义上说,可以通过激活 KCC2 介导的脊髓 GABA 信号通路来实现积极的效果。

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