JCNRJournal of Clinical and Nursing Research2208-36852208-3693Bio-Byword Scientific Publishing Pty. Ltd.10.26689/jcnr.v8i11.8923ArticleResearch Progress and Mechanisms of Acupuncture Combined with Transcutaneous Vagal Nerve Stimulation in the Treatment of Cognitive Impairment after Strokehttps://artdesignp.com/journal/JCNR/8/11/10.26689/jcnr.v8i11.8923YangShan,GongYongjie,WuKai,LeiHaoxing,YuYalan20248112024-11-27Cognitive impairment is a common complication after stroke, which not only affects the rehabilitation process of patients but also increases the family and socio-economic burden. Finding an effective treatment for cognitive impairment after stroke is urgent. Acupuncture can effectively activate blood circulation, dredge collaterals, tonify qi and blood, and regulate yin and yang. It is an effective method for the treatment of cognitive impairment after stroke. Recent studies have shown that acupuncture combined with various modern rehabilitation techniques, such as transcutaneous vagus nerve stimulation, has better clinical effects than either acupuncture or rehabilitation therapy alone. This article reviews the clinical research and basic mechanisms in this field by searching Chinese and English literature from the past 20 years, aiming to provide research ideas for future studies on the combined treatment of post-stroke cognitive impairment and related mechanisms.

Chinese Stroke Association, Experts Committee of Post-Stroke Cognitive Impairment, 2019, Guideline of Outpatient Management for Post-Stroke Cognitive Impairment. Chinese Journal of Stroke, 14(9): 909–922.

Wu S, Wu B, Liu M, et al., 2019, Stroke in China: Advances and Challenges in Epidemiology, Prevention, and Management. Lancet Neurol, 18(4): 394–405. https://doi.org/10.1016/S1474-4422(18)30500-3

Yu KH, Cho SJ, Oh MS, et al., 2013, Cognitive Impairment Evaluated with Vascular Cognitive Impairment Harmonization Standards in a Multicenter Prospective Stroke Cohort in Korea. Stroke, 44(3): 786–788. https://doi.org/10.1161/STROKEAHA.112.668343

Renjen PN, Gauba C, Chaudhari D, 2015, Cognitive Impairment After Stroke. Cureus, 7(9): e335. https://doi.org/10.7759/cureus.335

Xu MJ, Mu JP, Qiu LY, et al., 2021, Advances in Domestic and International Research on Post-Stroke Cognitive Impairment. Massage and Rehabilitation Medicine, 12(24): 73–78.

Li Y, Gu GF, Wang J, 2022, Research Progress on Post-Stroke Cognitive Impairment. Chinese Journal of Practical Neurological Diseases, 25(5): 647–651.

Wu H, 2023, Clinical Efficacy of Acupuncture Combined with Transcutaneous Vagus Nerve Stimulation in the Treatment of Post-Stroke Patients with Cognitive Impairment, dissertation, Tianjin University of Traditional Chinese Medicine.

Broncel A, Bocian R, Kłos-Wojtczak P, et al., 2020, Vagal Nerve Stimulation as a Promising Tool in the Improvement of Cognitive Disorders. Brain Res Bull, 155: 37–47. https://doi.org/10.1016/j.brainresbull.2019.11.011

Liu AF, Zhao FB, Wang J, et al., 2016, Effects of Vagus Nerve Stimulation on Cognitive Functioning in Rats with Cerebral Ischemia Reperfusion. J Transl Med, 14: 101. https://doi.org/10.1186/s12967-016-0858-0

Tu WJ, Zhao Z, Yin P, et al., 2023, Estimated Burden of Stroke in China in 2020. JAMA Netw Open, 6(3): e231455. https://doi.org/10.1001/jamanetworkopen.2023.1455

El Husseini N, Katzan IL, Rost NS, et al., 2023, Cognitive Impairment After Ischemic and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke, 54(6): e272–e291. https://doi.org/10.1161/STR.0000000000000430

Huang YY, Chen SD, Leng XY, et al., 2022, Post-Stroke Cognitive Impairment: Epidemiology, Risk Factors, and Management. J Alzheimers Dis, 86(3): 983–999. https://doi.org/10.3233/JAD-215644

Lo JW, Crawford JD, Desmond DW, et al., 2019, Profile of and Risk Factors for Poststroke Cognitive Impairment in Diverse Ethnoregional Groups. Neurology, 93(24): e2257–e2271. https://doi.org/10.1212/WNL.0000000000008612

Douiri A, Rudd AG, Wolfe CD, 2013, Prevalence of Poststroke Cognitive Impairment: South London Stroke Register 1995–2010. Stroke, 44(1): 138–145. https://doi.org/10.1161/STROKEAHA.112.670844

GBD 2019 Stroke Collaborators, 2021, Global, Regional, and National Burden of Stroke and Its Risk Factors, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet Neurol, 20(10): 795–820. https://doi.org/10.1016/S1474-4422(21)00252-0

Weng YH, Huang JH, Huang DH, 2019, Clinical Research Progress on Traditional Chinese Medicine in the Treatment of Vascular Dementia. Shandong Journal of Traditional Chinese Medicine, 38(1): 101–104.

Zhao TJ, Tang F, Wang WL, et al., 2017, Research Progress on Traditional Chinese Medicine in the Treatment of Vascular Dementia. Hunan Journal of Traditional Chinese Medicine, 33(11): 164–166.

Zhang Q, Li L, 2018, Clinical Research of Bagua-scalp Acupuncture on Mild Cognitive Impairment after Ischemic Stroke. Journal of Emergency in Traditional Chinese Medicine, 27(7): 1232–1234.

Cai Y, Zhang W, Wu J, 2024, Clinical Observation of Scalp Acupuncture Combined with Acupuncture at Back-Acupoints in Treating Mild to Moderate Cognitive Impairment after Stroke. China’s Naturopathy, 32(11): 73–76.

Zhang Z, 2023, Study on Acupuncture Therapy of Dredging Governor Vessel for Regulating Mentality in Post-Stroke Cognitive Impairment Non-Dementia, dissertation, Guangzhou University of Chinese Medicine.

Zhou C, Liu H, Yang Y, et al., 2018, Clinical Effect and Mechanism Research of Scalp Acupuncture for Mild Cognitive Impairment. China Journal of Traditional Chinese Medicine and Pharmacy, 33(6): 2464–2467.

Zhai Y, Su T, Song R, et al., 2023, Acupoint Selection Rules in Acupuncture and Moxibustion Treatment of Cognitive Impairment after Stroke Based on Data Mining Technology. World Chinese Medicine, 18(14): 2040–2044 + 2051.

Kang J, 2011, Clinical Study of Effect of Electroacupuncture on GV20 and EX-HN1 on Stroke Patients with Cognitive Impairment, dissertation, Fujian University of Traditional Chinese Medicine.

Han S, Li X, Wang Y, et al., 2024, Progress in Multimodal MRI Research on Acupuncture at Siguan Point for the Treatment of Mild Cognitive Impairment. Chinese Journal of Magnetic Resonance Imaging, 15(6): 138–143.

Wang L, Wang Z, Su L, et al., 2022, Regularity of Acupoint Selection in Treatment of Post-Stroke Cognitive Impairment (PSCI) with Acupuncture in Last 15 Years Based on Data Mining. World Chines Medicine, 17(3): 413–417 + 423.

Wang Z, 2021, Clinical Study of Abdominal Acupuncture on Post-Stroke Cognitive Impairment, dissertation, Shandong University of Traditional Chinese Medicine.

Gao J, Lu C, Yuan J, et al., 2023, Exploration of the Acupoint Selection Rules of Acupuncture and Moxibustion for Post-Stroke Cognitive Impairment Based on Data Mining. Journal of Guangzhou University of Traditional Chinese Medicine, 40(11): 2943–2949.

Bauer S, Baier H, Baumgartner C, et al., 2016, Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02). Brain Stimul, 9(3): 356–363. https://doi.org/10.1016/j.brs.2015.11.003

Frangos E, Ellrich J, Komisaruk BR, 2015, Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul, 8(3): 624–636. https://doi.org/10.1016/j.brs.2014.11.018

Baig SS, Kamarova M, Ali A, et al., 2022, Transcutaneous Vagus Nerve Stimulation (tVNS) in Stroke: The Evidence, Challenges and Future Directions. Auton Neurosci, 237: 102909. https://doi.org/10.1016/j.autneu.2021.102909

Báez-Pagán CA, Delgado-Vélez M, Lasalde-Dominicci JA, 2015, Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation. J Neuroimmune Pharmacol, 10(3): 468–476. https://doi.org/10.1007/s11481-015-9601-5

Pavlov VA, Tracey KJ, 2005, The Cholinergic Anti-Inflammatory Pathway. Brain Behav Immun, 19(6): 493–499. https://doi.org/10.1016/j.bbi.2005.03.015

Koo JW, Duman RS, 2008, IL-1beta is an Essential Mediator of the Antineurogenic and Anhedonic Effects of Stress. Proc Natl Acad Sci U S A, 105(2): 751–756. https://doi.org/10.1073/pnas.0708092105

Hasselmo ME, 2006, The Role of Acetylcholine in Learning and Memory. Curr Opin Neurobiol, 16(6): 710–715. https://doi.org/10.1016/j.conb.2006.09.002

Schultz W, 2007, Multiple Dopamine Functions at Different Time Courses. Annu Rev Neurosci, 30: 259–288. https://doi.org/10.1146/annurev.neuro.28.061604.135722

Huston JM, Ochani M, Rosas-Ballina M, et al., 2006, Splenectomy Inactivates the Cholinergic Antiinflammatory Pathway During Lethal Endotoxemia and Polymicrobial Sepsis. J Exp Med, 203(7): 1623–1628. https://doi.org/10.1084/jem.20052362

Pavlov VA, Tracey KJ, 2012, The Vagus Nerve and the Inflammatory Reflex–Linking Immunity and Metabolism. Nat Rev Endocrinol, 8(12): 743–754. https://doi.org/10.1038/nrendo.2012.189

Koopman FA, Chavan SS, Miljko S, et al., 2016, Vagus Nerve Stimulation Inhibits Cytokine Production and Attenuates Disease Severity in Rheumatoid Arthritis. Proc Natl Acad Sci U S A, 113(29): 8284–8289. https://doi.org/10.1073/pnas.1605635113

Rosas-Ballina M, Olofsson PS, Ochani M, et al., 2011, Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit. Science, 334(6052): 98–101. https://doi.org/10.1126/science.1209985

Wang J, Liu P, Liu C, et al., 2022, Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Patients’ Early-stage Post-operative Cognitive Function. Shanghai Journal of Acupuncture and Moxibustion, 41(5): 454–459.

Jin R, Yang G, Li G, 2010, Inflammatory Mechanisms in Ischemic Stroke: Role of Inflammatory Cells. J Leukoc Biol, 87(5): 779–789. https://doi.org/10.1189/jlb.1109766

Narasimhalu K, Lee J, Leong YL, et al., 2015, Inflammatory Markers and Their Association with Post Stroke Cognitive Decline. Int J Stroke, 10(4): 513–518. https://doi.org/10.1111/ijs.12001

Kliper E, Bashat DB, Bornstein NM, et al., 2013, Cognitive Decline After Stroke: Relation to Inflammatory Biomarkers and Hippocampal Volume. Stroke, 44(5): 1433–1435. https://doi.org/10.1161/STROKEAHA.111.000536

Kulesh A, Drobakha V, Kuklina E, et al., 2018, Cytokine Response, Tract-Specific Fractional Anisotropy, and Brain Morphometry in Post-Stroke Cognitive Impairment. J Stroke Cerebrovasc Dis, 27(7): 1752–1759. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.004

Qi S, Fan Y, Tang Y, et al., 2021, Effects of Percutaneous Non-Invasive Vagus Nerve Stimulation on Postoperative Cognitive Functions in Elderly Orthopedic Patients. Shanghai Medical Journal, 44(11): 827–831.

Li YG, Zhou S, Wei XM, et al., 2022, Effect of Vagus Nerve Electrical Stimulation on Learning and Memory Ability in Epileptic Rats Through α7nAChR Regulation of Microglial Activation. Chinese Journal of Neuroimmunology and Neurology, 29(6): 511–514.

Ahmed Z, Shaw G, Sharma VP, et al., 2007, Actin-Binding Proteins Coronin-1a and IBA-1 are Effective Microglial Markers for Immunohistochemistry. J Histochem Cytochem, 55(7): 687–700. https://doi.org/10.1369/jhc.6A7156.2007

Zhang F, 2017, The Relationship between Epileptic Seizures and Inflammatory Reaction and Its Influence on Cognitive Function in Rats, dissertation, Lanzhou University.

Vaynman S, Gomez-Pinilla F, 2005, License to Run: Exercise Impacts Functional Plasticity in the Intact and Injured Central Nervous System by Using Neurotrophins. Neurorehabil Neural Repair, 19(4): 283–295. https://doi.org/10.1177/1545968305280753

Nithianantharajah J, Hannan AJ, 2006, Enriched Environments, Experience-Dependent Plasticity and Disorders of the Nervous System. Nat Rev Neurosci, 7(9): 697–709. https://doi.org/10.1038/nrn1970

Kolb B, Gibb R, 2011, Brain Plasticity and Behaviour in the Developing Brain. J Can Acad Child Adolesc Psychiatry, 20(4): 265–276.

Xiong J, Zhang Z, Ma Y, et al., 2020, The Effect of Combined Scalp Acupuncture and Cognitive Training in Patients with Stroke on Cognitive and Motor Functions. NeuroRehabilitation, 46(1): 75–82. https://doi.org/10.3233/NRE-192942

Wang Z, Su L, 2021, Study on the Rules of Acupoint Selection in Acupuncture Treatment of Post-stroke Cognitive Function Impairment Based on Data Mining. Western Journal of Traditional Chinese Medicine, 34(6): 75–80.

Sun P, Cai R, Li P, et al., 2019, Protective Effects on Hippocampal Neurons and the Influence on Hippocampal Monoamine Neurotransmitters with Acupuncture for Promoting the Circulation of the Governor Vessel and Regulating the Mental State in Rats with Post-Stroke Depression. Chinese Acupuncture & Moxibustion, 39(7): 741–747.

Mu H, Tang J, Huang H, et al., 2023, Systematic Evaluation of Acupuncture Combined with Cognitive Training for the Treatment of Post-stroke Cognitive Impairment. Neural Injury and Functional Reconstruction, 18(7): 373–379.

Liu R, Yu X, Wang J, et al., 2020, Evaluation of the Efficacy and Safety of the Use of Acupuncture for the Adjuvant Treatment of Patients with Post-Stroke Cognitive Impairment: Protocol for a Randomized Controlled Trial. Trials, 21(1): 753. https://doi.org/10.1186/s13063-020-04656-w

Hung CY, Wu XY, Chung VC, et al., 2019, Overview of Systematic Reviews with Meta-Analyses on Acupuncture in Post-Stroke Cognitive Impairment and Depression Management. Integr Med Res, 8(3): 145–159. https://doi.org/10.1016/j.imr.2019.05.001

Vacas S, Degos V, Feng X, et al., 2013, The Neuroinflammatory Response of Postoperative Cognitive Decline. Br Med Bull, 106(1): 161–178. https://doi.org/10.1093/bmb/ldt006

Huffman WJ, Subramaniyan S, Rodriguiz RM, et al., 2019, Modulation of Neuroinflammation and Memory Dysfunction Using Percutaneous Vagus Nerve Stimulation in Mice. Brain Stimul, 12(1): 19–29. https://doi.org/10.1016/j.brs.2018.10.005

Khodaparast N, Kilgard MP, Casavant R, et al., 2016, Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats. Neurorehabil Neural Repair, 30(7): 676–684. https://doi.org/10.1177/1545968315616494

Jiang Y, Li L, Tan X, et al., 2015, miR-210 Mediates Vagus Nerve Stimulation-Induced Antioxidant Stress and Anti-Apoptosis Reactions Following Cerebral Ischemia/Reperfusion Injury in Rats. J Neurochem, 134(1): 173–181. https://doi.org/10.1111/jnc.13097

Zhang L, Ma J, Jin X, et al., 2017, L-PGDS Mediates Vagus Nerve Stimulation-Induced Neuroprotection in a Rat Model of Ischemic Stroke by Suppressing the Apoptotic Response. Neurochem Res, 42(2): 644–655. https://doi.org/10.1007/s11064-016-2121-8

Li J, Zhang K, Zhang Q, et al., 2020, PPAR-γ Mediates Ta-VNS-Induced Angiogenesis and Subsequent Functional Recovery after Experimental Stroke in Rats. Biomed Res Int, 2020: 8163789. https://doi.org/10.1155/2020/8163789

Yang H, Bai Q, 2023, Research Progress in the Treatment of Post-Stroke Cognitive Impairment. China Modern Medicine, 30(2): 42–45.