Electroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei.

As a traditional medical therapy, stimulation at the Lianquan (CV23) acupoint, located at the depression superior to the hyoid bone, has been shown to be beneficial in dysphagia. However, little is known about the neurological mechanism by which this peripheral stimulation approach treats for dysphagia. Here, we first identified a cluster of excitatory neurons in layer 5 (L5) of the primary motor cortex (M1) that can regulate swallowing function in male mice by modulating mylohyoid activity. Moreover, we found that focal ischemia in the M1 mimicked the post-stroke dysphagia (PSD) pathology, as indicated by impaired water consumption and electromyographic responses in the mylohyoid. This dysfunction could be rescued by electroacupuncture (EA) stimulation at the CV23 acupoint (EA-CV23) in a manner dependent on the excitatory neurons in the contralateral M1 L5. Furthermore, neuronal activation in both the parabrachial nuclei (PBN) and nucleus tractus solitarii (NTS), which was modulated by the M1, was required for the ability of EA-CV23 treatment to improve swallowing function in male PSD model mice. Together, these results uncover the importance of the M1-PBN-NTS neural circuit in driving the protective effect of EA-CV23 against swallowing dysfunction and thus reveal a potential strategy for dysphagia intervention.

Effect of Electro-Acupuncture on Lateralization of the Human Swallowing Motor Cortex Excitability by Navigation-Transcranial Magnetic Stimulation-Electromyography.

Background: The use of transcranial magnetic stimulation combined with electromyography for the functional evaluation of the cerebral cortex in both clinical and non-clinical populations is becoming increasingly common. Numerous studies have shown that electro-acupuncture (EA) can regulate cerebral cortical excitability. However, the effect of EA on the lateralization of the human swallowing motor cortex excitability is not yet fully understood. Objective: The aim of this study was to assess whether lateralization is present in the swallowing motor cortex of healthy subjects, and to investigate the impact of EA at Lianquan (CV23) and Fengfu (GV16) on lateralization. Methods: Forty subjects were randomized 1:1 into the EA group and the sham-EA group. The bilateral swallowing motor cortices was located by a neuroimaging navigation system. Then, the resting motor threshold (RMT) and motor evoked potential (MEP) of the mylohyoid of healthy subjects were recorded while applying combined transcranial magnetic stimulation and electromyography before and after EA or sham-EA. Results: First, the RMT and MEP latency of the contralateral mylohyoid innervated by the right swallowing cortex (71.50 ± 1.67%, 8.30 ± 0.06 ms) were lower than those innervated by the left (79.38 ± 1.27%, 8.40 ± 0.06 ms). Second, EA at CV23 and GV16 reduced the bilateral RMT and enhanced the bilateral MEP latency and amplitude (P = 0.005, P < 0.001; P = 0.002, P = 0.001; P = 0.002, P = 0.009), while sham-EA did not (P > 0.05). Third, EA had an effect on the RMT and MEP latency in terms of lateralization changes, but this was not significant (P = 0.067, P = 0.156). Conclusion: The right swallowing motor cortex of healthy subjects is more excitable than that of the left at resting state. Thus, we found that lateralization is present in the swallowing motor cortex of healthy people, which might indicate a hemispheric dominance of swallowing predominates in the right swallowing motor cortex. In addition, EA at CV23 and GV16 can instantly promote the excitability of the bilateral swallowing motor cortices. But there was no significant difference in EA stimulation in terms of lateralization.

Electroacupuncture Involved in Motor Cortex and Hypoglossal Neural Control to Improve Voluntary Swallowing of Poststroke Dysphagia Mice.

The descending motor nerve conduction of voluntary swallowing is mainly launched by primary motor cortex (M1). M1 can activate and regulate peripheral nerves (hypoglossal) to control the swallowing. Acupuncture at "Lianquan" acupoint (CV23) has a positive effect against poststroke dysphagia (PSD). In previous work, we have demonstrated that electroacupuncture (EA) could regulate swallowing-related motor neurons and promote swallowing activity in the essential part of central pattern generator (CPG), containing nucleus ambiguus (NA), nucleus of the solitary tract (NTS), and ventrolateral medulla (VLM) under the physiological condition. In the present work, we have investigated the effects of EA on the PSD mice in vivo and sought evidence for PSD improvement by electrophysiology recording and laser speckle contrast imaging (LSCI). Four main conclusions can be drawn from our study: (i) EA may enhance the local field potential in noninfarction area of M1, activate the swallowing-related neurons (pyramidal cells), and increase the motor conduction of noninfarction area in voluntary swallowing; (ii) EA may improve the blood flow in both M1 on the healthy side and deglutition muscles and relieve PSD symptoms; (iii) EA could increase the motor conduction velocity (MCV) in hypoglossal nerve, enhance the EMG of mylohyoid muscle, alleviate the paralysis of swallowing muscles, release the substance P, and restore the ability to drink water; and (iv) EA can boost the functional compensation of M1 in the noninfarction side, strengthen the excitatory of hypoglossal nerve, and be involved in the voluntary swallowing neural control to improve PSD. This research provides a timely and necessary experimental evidence of the motor neural regulation in dysphagia after stroke by acupuncture in clinic.

Effect of Different Frequencies of Electroacupuncture on Post-Stroke Dysphagia in Mice.

The aim of this study was to determine the optimum frequency of electroacupuncture (EA) for the treatment of dysphagia after stroke. Male C57BL/6 J mice were randomly divided into five groups: normal, model, 2 Hz, 50 Hz, and 100 Hz groups. All mice received a photochemical ischemia, except the normal group. The EA parameters were 1 mA for 15 min, with different frequencies (2, 50, and 100 Hz) applied. After a three day treatment, neuronal activation was detected by the expression of c-Fos. A multi-channel electrophysiological technique was used to assess the discharge of contralateral neurons and the neuron types in each group. The concentration of brain-derived neurotrophic factor (BDNF) in the contralateral neurons was also examined. In addition, the dysfunction of swallowing in mice was calculated according to the lick counts and the lick-lick interval within a certain period of time. The number of c-Fos neurons (P < 0.05) and the expression of BDNF (P < 0.05) increased after the 2 Hz EA treatment. The total frequency of neuron discharge in the 2 Hz group increased compared with the model group (P < 0.05). The pattern of sorted neuron populations was similar between the normal and 2 Hz groups. Consistent with these results, the lick counts increased (P < 0.05) and the lick-lick interval decreased after the 2 Hz EA treatment, which indicated a functional improvement in swallowing. These results indicated that the 2 Hz EA treatment had a good effect on dysphagia after stroke.

[Development of research on mechanisms of electroacupuncture intervention underlying improvement of cerebral ischemia rats in recent five years].

In the present paper, we summarized the relevant research literature on the underlying mechanism of electroacupuncture (EA) intervention in improving cerebral ischemia (CI) in middle cerebral artery occlusion (MCAO) model rats in recent 5 years from preconditioning and regular intervention. Outcomes showed that both EA preconditioning and regular intervention could relieve CI by reducing toxicity of excitatory amino acids (glutamate, aspartate) and TLR4/NF-κB-mediated inflammatory cascade reaction to relieve inflammatory injury. Moreover, EA preconditioning also could suppress the expression of pro-apoptosis genes and proteins to relieve apoptosis, regulate activation of microglia, and down-regulate the expression of blood brain barrier integrity-related matrix metalloprotein 9. Regular EA intervention also could promote angiogenesis to increase supply of blood and oxygen, facilitate regeneration, proliferation and differentiation of neural stem cells via triggering activation of Notch and Shh signaling pathways, and promote the secretion of neurotrophin by up-regulating the expression of brain derived neurotrophic factor and nerve growth factor /Trk A receptor, and promote expression of axon growth and synaptic remodeling-related factor (Ephrin B2/Eph B2) and sr-GTPase activating protein 1 and cell division cycle 42 (Cdc42, axon growth and orientated down-stream molecules). However, up to now, the conclusion is still fragmentary and one-sided, and can not explain the specific mechanism of electroacupuncture in MCAO rats, needing further in-depth study.