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Vagus Nerve Stimulation in Ischemic Stroke

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Abstract

Purpose of Review

Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms.

Recent Findings

Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery.

Summary

The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.

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Data Availability

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Abbreviations

ABVN:

Auricular branch of the vagus nerve

AIS:

Acute ischemic stroke

BBB:

Blood–brain barrier

BDNF:

Brain-derived neurotrophic factor

CSD:

Cortical spreading depolarization

FDA:

Food and Drug Administration

GDF11:

Growth differentiation factor 11

ICH:

Intracerebral hemorrhage

LC:

Locus coeruleus

LC3:

Light chain 3

L-PGDS:

Lipocalin-type prostaglandin D synthase

IL:

Interleukin

MCAo:

Middle cerebral artery occlusion

mRS:

Modified Rankin scale

NIHSS:

National Institute of Health stroke scale

NTS:

Nucleus tractus solitarius

nVNS:

Non-invasive vagus nerve stimulation

PPAR-γ:

Peroxisome proliferator-activated receptor-gamma

rIL-17A:

Recombinant IL-17A

TBI:

Traumatic brain injury

taVNS:

Transcutaneous auricular vagus nerve stimulation

tcVNS:

Transcutaneous cervical vagus nerve stimulation

VEGF:

Vascular endothelial growth factor

VNS:

Vagus nerve stimulation

α7nAChR:

α7 Nicotinic acetylcholine receptor subunit

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Authors and Affiliations

  1. Research Unit of Neurology, Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

    Sasan Andalib

  2. Department of Neurology, Odense University Hospital, Odense, Denmark

    Sasan Andalib

  3. Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, USA

    Afshin A. Divani & Masoom J. Desai

  4. Neurovascular Research Unit, Department of Radiology and Stroke Service, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    Cenk Ayata

  5. Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK

    Sheharyar Baig & Arshad Majid

  6. Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Ethem Murat Arsava & Mehmet Akif Topcuoglu

  7. Department of Critical Care, Clínica de La Universidad de La Sabana, Chía, Colombia

    Eder Leonardo Cáceres

  8. Department of Psychology and Neuroscience, Temple University, Philadelphia, PA, USA

    Vinay Parikh

  9. Neurological Service, SS Annunziata Hospital, Sulmona, L’Aquila, Italy

    Sara Girolami & Mario Di Napoli

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Correspondence to Afshin A. Divani.

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Sasan Andalib, Cenk Ayata, Ethem Murat Arsava, Mehmet Akif Topcuoglu, Eder Leonardo Cáceres, Vinay Parikh, Masoom J Desai, Sara Girolami, and Mario Di Napoli each declare no potential conflicts of interest.

Afshin A. Divani is supported by the National Institute of Neurological Disorders and Stroke (NINDS) grant # 1R21NS130423-01.

Sheharyar Baig is supported by the Association of British Neurologists Clinical Research Training Fellowship (co-funded by the Stroke Association and Berkeley Foundation). Sheharyar Baig and Arshad Majid are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre, Sheffield, England. The expressed views are those of the authors and not necessarily those of the NINDS, the National Health Service (NHS), the NIHR, or the Department of Health and Social Care (DHSC).

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Andalib, S., Divani, A.A., Ayata, C. et al. Vagus Nerve Stimulation in Ischemic Stroke. Curr Neurol Neurosci Rep 23, 947–962 (2023). https://doi.org/10.1007/s11910-023-01323-w

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