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image of Electroacupuncture Intervention Improves Post-Stroke Dysphagia by 
Modulating NMDAR1 and GABABR1

Abstract

Introduction

Post-stroke dysphagia (PSD) is a common complication after acute stroke. It can be effectively alleviated by electroacupuncture (EA) stimulation at the Baihui acupoint; however, the underlying mechanism remains unclear.

Methods

Male ICR mice were used, and the suture occlusion method was employed to establish the middle cerebral artery occlusion (MCAO) mouse model. EA stimulation was applied to the Baihui acupoint for intervention. After treatment, the survival rate of the mice was assessed. Subsequently, a water swallow test was conducted to evaluate the degree of dysphagia in the mice. Additionally, neurological function was assessed through Garcia scoring and measurement of serum Ca2+-Mg2+-ATPase activity. Fur-thermore, MRI was utilized to evaluate the therapeutic effects of EA on cerebral infarction and edema rates. Then, the antioxidant activity of the EA intervention was assessed by measuring indicators of oxida-tive damage. Finally, the expressions of gamma-aminobutyric acid type B receptor subunit 1 (GAB-ABR1), N-methyl-D-aspartate receptor 1 (NMDAR1) were detected through WB, RT-qPCR, and immu-nofluorescence.

Results

EA intervention effectively increased the survival rate of MCAO mice and alleviated their dysphagia. Additionally, the impaired neurological function of the mice was improved, and cerebral infarction and edema rates were reduced. Furthermore, EA alleviated oxidative stress in mice, reduced damage to neurons in the nucleus ambiguus, and upregulated GABABR1 while downregulating NMDAR1.

Discussion

Although we suggested that EA may exert therapeutic activity for PSD by maintaining the balance of NMDAR1 and GABABR1, this conclusion still requires further experimental validation.

Conclusion

EA stimulation of the Baihui acupoint was effective in treating PSD, which was related to its ability to improve damaged neurons, upregulate GABABR1, and downregulate NMDAR1. These findings provided a new insight into the mechanisms of EA treatment for PSD and serve as a theoretical basis for future clinical research.

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2025-08-11
2025-12-16
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References

  1. Hurd M.D. Goel I. Sakai Y. Teramura Y. Current status of ischemic stroke treatment: From thrombolysis to potential regenerative medicine. Regen. Ther. 2021 18 408 417 10.1016/j.reth.2021.09.009 34722837
    [Google Scholar]
  2. Ding Q. Liu S. Yao Y. Liu H. Cai T. Han L. Global, regional, and national burden of ischemic stroke, 1990–2019. Neurology 2022 98 3 e279 e290 10.1212/WNL.0000000000013115 34911748
    [Google Scholar]
  3. Rofes L. Muriana D. Palomeras E. Vilardell N. Palomera E. Alvarez-Berdugo D. Casado V. Clavé P. Prevalence, risk factors and complications of oropharyngeal dysphagia in stroke patients: A cohort study. Neurogastroenterol. Motil. 2018 30 8 e13338 10.1111/nmo.13338 29573064
    [Google Scholar]
  4. Xu Z. Gu Y. Li J. Wang C. Wang R. Huang Y. Zhang J. Dysphagia and aspiration pneumonia in elderly hospitalization stroke patients: Risk factors, cerebral infarction area comparison. J. Back Musculoskeletal Rehabil. 2019 32 1 85 91 10.3233/BMR‑170801 30223382
    [Google Scholar]
  5. Dziewas R. Michou E. Trapl-Grundschober M. Lal A. Arsava E.M. Bath P.M. Clavé P. Glahn J. Hamdy S. Pownall S. Schindler A. Walshe M. Wirth R. Wright D. Verin E. European stroke organisation and european society for swallowing disorders guideline for the diagnosis and treatment of post-stroke dysphagia. Eur. Stroke J. 2021 6 3 LXXXIX CXV 10.1177/23969873211039721 34746431
    [Google Scholar]
  6. Doan T.N. Ho W.C. Wang L.H. Chang F.C. Tran T.T.Q. Chou L.W. Therapeutic effect and optimal electrode placement of transcutaneous neuromuscular electrical stimulation in patients with post-stroke dysphagia: A systematic review and meta-analysis of randomized controlled trials. Life 2022 12 6 875 10.3390/life12060875 35743906
    [Google Scholar]
  7. Fang W. Zheng F. Zhang L. Wang W. Yu C. Shao J. Wu Y. Research progress of clinical intervention and nursing for patients with post-stroke dysphagia. Neurol. Sci. 2022 43 10 5875 5884 10.1007/s10072‑022‑06191‑9 35661279
    [Google Scholar]
  8. Yao L. Liang W. Du X. Chen Y. Huang X. Effect of acupuncture on long-term outcomes in patients with post-stroke dysphagia. NeuroRehabilitation 2022 51 3 433 441 10.3233/NRE‑220113 35871375
    [Google Scholar]
  9. Li N. Wang H. Liu H. Zhu L. Lyu Z. Qiu J. Zhao T. Ren H. Huang L. Chen S. Hu X. Zhou L. The effects and mechanisms of acupuncture for post-stroke cognitive impairment: Progress and prospects. Front. Neurosci. 2023 17 1211044 10.3389/fnins.2023.1211044 37397457
    [Google Scholar]
  10. Xu Z.J. Wu L.N. Xu F. Li G.P. Wang S. Ye Y.Z. Acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy based on data mining technology. Zhongguo Zhenjiu 2023 43 6 715 720 10.13703/j.0255‑2930.20220911‑k0004 37313568
    [Google Scholar]
  11. Chen S.Y. Zou D.H. Zheng S.J. A brief discussion on the theoretical basis and mechanism of action of baihui-to-bone therapy for transient ischemic attack. Clin. Res. Chinese Med. 2022 14 33 52 55
    [Google Scholar]
  12. Wang Y. Wang J. Research progress on the treatment of post-stroke sequelae with prolonged needle retention at baihui acupoint. Clin. J. Chin. Med. Pharm. 2022 34 8 1559 1563 10.16448/j.cjtcm.2022.0843
    [Google Scholar]
  13. Blount Q. Hernandez-Morato I. Moayedi Y. Pitman M.J. Expression of glial cell‐derived neurotrophic factor receptors within nucleus ambiguus during rat development. Laryngoscope 2023 133 9 2240 2247 10.1002/lary.30440 36271908
    [Google Scholar]
  14. Fogarty M.J. Dendritic morphology of motor neurons and interneurons within the compact, semicompact, and loose formations of the rat nucleus ambiguus. Front. Cell. Neurosci. 2024 18 1409974 10.3389/fncel.2024.1409974 38933178
    [Google Scholar]
  15. Ahmadi F. Zendehdel M. Babapour V. Panahi N. Hassanpour S. Khodadadi M. Modulatory function of NMDA glutamate receptor on MC3/MC4 receptors agonist-induced hypophagia in neonatal meat-type chicken. Vet. Res. Commun. 2017 41 4 241 248 10.1007/s11259‑017‑9693‑x 28589422
    [Google Scholar]
  16. Shi J. Ye Q. Zhao J. Liu J. Xu Z. Yi W. Xu N. EA promotes swallowing via activating swallowing-related motor neurons in the nucleus ambiguus. Brain Res. 2019 1718 103 113 10.1016/j.brainres.2018.12.013 30537518
    [Google Scholar]
  17. Urrutia P.J. González-Billault C. A role for second messengers in axodendritic neuronal polarity. J. Neurosci. 2023 43 12 2037 2052 10.1523/JNEUROSCI.1065‑19.2023 36948585
    [Google Scholar]
  18. Kumar V.S. Gopalakrishnan A. Naziroğlu M. Rajanikant G.K. Calcium ion--the key player in cerebral ischemia. Curr. Med. Chem. 2014 21 18 2065 2075 10.2174/0929867321666131228204246 24372212
    [Google Scholar]
  19. Letellier M. Goda Y. Astrocyte calcium signaling shifts the polarity of presynaptic plasticity. Neuroscience 2023 525 38 46 10.1016/j.neuroscience.2023.05.032 37295597
    [Google Scholar]
  20. Chen B. Lin W. Li Z. Zhong X. Wang J. You X. Zhao H. Qi D. Electroacupuncture attenuates ischemic brain injury and cellular apoptosis via mitochondrial translocation of cofilin. Chin. J. Integr. Med. 2021 27 9 705 712 10.1007/s11655‑021‑3335‑4 33709239
    [Google Scholar]
  21. Chuang C.M. Hsieh C.L. Li T.C. Lin J.G. Acupuncture stimulation at Baihui acupoint reduced cerebral infarct and increased dopamine levels in chronic cerebral hypoperfusion and ischemia-reperfusion injured sprague-dawley rats. Am. J. Chin. Med. 2007 35 5 779 791 10.1142/S0192415X07005260 17963318
    [Google Scholar]
  22. Su K. Hao W. Lv Z. Wu M. Li J. Hu Y. Zhang Z. Gao J. Feng X. Electroacupuncture of Baihui and Shenting ameliorates cognitive deficits via Pten/Akt pathway in a rat cerebral ischemia injury model. Front. Neurol. 2022 13 855362 10.3389/fneur.2022.855362 36062010
    [Google Scholar]
  23. Muscari A. Falcone R. Pirazzoli E. Faccioli L. Muscari S. Pastore Trossello M. Puddu G.M. Rignanese L. Spinardi L. Zoli M. Predicting failure to recover swallowing in patients with severe post-stroke dysphagia: The DIsPHAGIc Score. Dysphagia 2023 38 1 290 304 10.1007/s00455‑022‑10467‑9 35676540
    [Google Scholar]
  24. Cui S. Yao S. Wu C. Yao L. Huang P. Chen Y. Tang C. Xu N. Electroacupuncture involved in motor cortex and hypoglossal neural control to improve voluntary swallowing of poststroke dysphagia mice. Neural Plast. 2020 2020 1 18 10.1155/2020/8857543 33061953
    [Google Scholar]
  25. Zhao H. Jiang Y. Wang S. He F. Ren F. Zhang Z. Yang X. Zhu C. Yue J. Li Y. Liu Y. Dysphagia diagnosis system with integrated speech analysis from throat vibration. Expert Syst. Appl. 2022 204 117496 10.1016/j.eswa.2022.117496
    [Google Scholar]
  26. Honzel E. Hernandez-Morato I. Joshi A. Pennington-Fitzgerald W. Moayedi Y. Pitman M.J. Temporal expression of Hox genes and Phox2b in the rat nucleus ambiguus during development: Implications on laryngeal innervation. Laryngoscope 2023 133 12 3462 3471 10.1002/lary.30826 37350386
    [Google Scholar]
  27. Belousov A. Fontes J. Role of neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemic neuronal death. Neural Regen. Res. 2016 11 1 75 76 10.4103/1673‑5374.169630 26981086
    [Google Scholar]
  28. Nguyen Q.N.S. Yoo K.Y. Pham T.T.T. Selvaraj B. Vu H.T. Le T.T. Lee H. Tran Q.L. Thuong P.T. Pae A.N. Jung S.H. Lee J.W. Neuroprotective effects of ethanol extract Polyscias guilfoylei (EEPG) against glutamate induced neurotoxicity in HT22 cells. Int. J. Mol. Sci. 2024 25 22 12153 10.3390/ijms252212153 39596219
    [Google Scholar]
  29. Schieweck R. Kiebler M.A. Posttranscriptional gene regulation of the GABA receptor to control neuronal inhibition. Front. Mol. Neurosci. 2019 12 152 10.3389/fnmol.2019.00152 31316346
    [Google Scholar]
  30. Abolghasempour S. Zendehdel M. Panahi N. Jahandideh A. Gilanpour H. Intracerebroventricular Injection of the Glutamatergic Receptors Antagonist Affects N/OFQ-Induced Hyperphagia in Neonatal Broilers: Role of NMDA and AMPA Receptors. Int. J. Pept. Res. Ther. 2019 25 3 835 843 10.1007/s10989‑018‑9733‑6
    [Google Scholar]
  31. Hung J.S. Liang S.W. Omari T. Wong M.W. Lei W.Y. Yi C.H. Liu T.T. Lin L. Chen C.L. Effects of the GABA (B) agonist baclofen on volitional swallowing in normal subjects. Kaohsiung J. Med. Sci. 2023 39 1 80 86 10.1002/kjm2.12607 36245436
    [Google Scholar]
  32. Yuan Y. Tian Y. Jiang H. Cai L. Song J. Peng R. Zhang X. Mechanism of PGC-1α-mediated mitochondrial biogenesis in cerebral ischemia–reperfusion injury. Front. Mol. Neurosci. 2023 16 1224964 10.3389/fnmol.2023.1224964 37492523
    [Google Scholar]
  33. Qian J. Liang T. Xu Y. Liu Z.P. Jing L.L. Luo H.B. Effect of the novel free radical scavenger 4′-hydroxyl-2-substituted phenylnitronyl nitroxide on oxidative stress, mitochondrial dysfunction and apoptosis induced by cerebral ischemia–reperfusion in rats. Neuroscience 2024 540 1 11 10.1016/j.neuroscience.2023.12.016 38242279
    [Google Scholar]
  34. Kong X.Y. Guan J. Wang R.Z. Molecular biological roles of oxidative stress in acute brain ischemia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2016 38 2 222 227 10.3881/j.issn.1000‑503X.2016.02.017 27181902
    [Google Scholar]
  35. Liu J. Jiang X. Zhang Q. Lin S. Zhu J. Zhang Y. Du J. Hu X. Meng W. Zhao Q. Neuroprotective effects of Kukoamine A against cerebral ischemia via antioxidant and inactivation of apoptosis pathway. Neurochem. Int. 2017 107 191 197 10.1016/j.neuint.2016.12.024 28088348
    [Google Scholar]
  36. Park U.J. Lee Y.A. Won S.M. Lee J.H. Kang S.H. Springer J.E. Lee Y.B. Gwag B.J. Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat. Acta Neuropathol. 2011 121 4 459 473 10.1007/s00401‑010‑0785‑8 21120509
    [Google Scholar]
  37. Shah F.A. Kury L.A. Li T. Zeb A. Koh P.O. Liu F. Zhou Q. Hussain I. Khan A.U. Jiang Y. Li S. Polydatin attenuates neuronal loss via reducing neuroinflammation and oxidative stress in rat MCAO models. Front. Pharmacol. 2019 10 663 10.3389/fphar.2019.00663 31293416
    [Google Scholar]
  38. Sun Y. Cheng M. Liang X. Chen S. Wang M. Zhang X. JAK2/STAT3 involves oxidative stress-induced cell injury in N2a cells and a rat MCAO model. Int. J. Neurosci. 2020 130 11 1142 1150 10.1080/00207454.2020.1730829 32064985
    [Google Scholar]
  39. Spohr L. Soares M.S.P. Bona N.P. Pedra N.S. Barschak A.G. Alvariz R.M. Vizzotto M. Lencina C.L. Stefanello F.M. Spanevello R.M. Effect of blueberry extract on energetic metabolism, levels of brain-derived neurotrophic factor, and Ca2+-ATPase activity in the hippocampus and cerebral cortex of rats submitted to ketamine-induced mania-like behavior. Metab. Brain Dis. 2022 37 3 835 847 10.1007/s11011‑022‑00904‑x 35043268
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: baihui point ; NMDAR1 ; electroacupuncture ; GABABR1 ; Post-stroke dysphagia ; neuronal damage
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