Non-invasive Vagus Nerve Stimulation Reduces Blood-brain Barrier Disruption in a Rat Model of Ischemic Stroke

Overview

Journal Brain Stimul

Publisher Elsevier

Specialty Neurology

Date 2018 Mar 3

PMID 29496430

Citations 55

Authors

Yirong Yang

Lisa Y Yang

Lilla Orban

Darnell Cuylear

Jeffrey Thompson

Bruce Simon

Yi Yang

Affiliations

Soon will be listed here.

Abstract

Background: Vagus nerve stimulation (VNS) significantly reduces infarct volume in rat models of cerebral ischemia, but the mechanism of this protective effect remains open.

Hypothesis: This study tested the hypothesis that non-invasive VNS (nVNS), during transient middle cerebral artery occlusion (MCAO), protects the blood-brain barrier (BBB), leading to reduced infarct size in ischemic brain.

Methods: Spontaneous hypertensive rats (SHRs) were subjected to a 90 min MCAO. nVNS treated rats received 5 stimulations (duration: 2 min; every 10 min) on the skin overlying the cervical vagus nerve in the neck beginning 30 min after MCAO onset. Control rats received the same stimulations on the quadriceps femoris muscle. Twenty-four hours after MCAO onset, MRI and immunohistochemistry (IHC) were performed for analyses of infarct size and BBB leakage.

Results: Compared with the control group, anatomic MRI T2-weighted images showed significantly smaller infarct sizes in the nVNS group. Dynamic contrast-enhanced (DCE)-MRI showed a significantly decreased BBB transfer rate (Ki map) in the lesion area in the nVNS group, which was spatially correlated with the attenuation of the infarct size. Furthermore, significantly lower serum IgG leakage, visualized by IHC, was seen in the ischemic hemisphere in nVNS treated rats. nVNS also protected vascular tight junction proteins from disruption in microvessels, and reduced expression of matrix metalloproteinases-2/9 in reactive astrocytes surrounding the compromised vessels in the ischemic hemispheres.

Conclusion: Our data suggest that the neuroprotective role of a series of nVNS administrations during MCA occlusion, spatially correlates with protection of BBB integrity from damage and reduction of infarct extent induced by ischemic stroke.

Citing Articles

Mechanism and Applications of Vagus Nerve Stimulation.

Chen Z, Liu K Curr Issues Mol Biol. 2025; 47(2).

PMID: 39996843 PMC: 11854789. DOI: 10.3390/cimb47020122.

Case report: Monitoring consciousness with fNIRS in a patient with prolonged reduced consciousness following hemorrhagic stroke undergoing adjunct taVNS therapy.

Gao F, Wang L, Wang Z, Tian Y, Wu J, Wang M Front Neurosci. 2025; 19:1519939.

PMID: 39967804 PMC: 11832507. DOI: 10.3389/fnins.2025.1519939.

Noninvasive Vagus Nerve Stimulation Protects Neurons in the Perihematomal Region and Improves the Outcomes in a Rat Model of Intracerebral Hemorrhage.

Caceres E, Salazar P, Shidoh S, Ortiz M, Bragin D, Kibria F Neurocrit Care. 2025; .

PMID: 39815107 DOI: 10.1007/s12028-024-02195-9.

Transcutaneous Non-Invasive Vagus Nerve Stimulation: Changing the Paradigm for Stroke and Atrial Fibrillation Therapies?.

Forster C Biomolecules. 2025; 14(12.

PMID: 39766218 PMC: 11673676. DOI: 10.3390/biom14121511.

Vagus nerve stimulation: a physical therapy with promising potential for central nervous system disorders.

Wang C, Wu B, Lin R, Cheng Y, Huang J, Chen Y Front Neurol. 2024; 15:1516242.

PMID: 39734634 PMC: 11671402. DOI: 10.3389/fneur.2024.1516242.

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