Effects of Vagus Nerve Stimulation on Cognitive Functioning in Rats with Cerebral Ischemia Reperfusion

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2016 Apr 28

PMID 27118204

Citations 31

Authors

Ai-Fen Liu

Feng-bo Zhao

Jing Wang

Yi-Fan Lu

Jian Tian

Yin Zhao

Yan Gao

Xia-jun Hu

Xiao-Yan Liu

Jie Tan

Yun-li Tian

Jing Shi

Affiliations

Soon will be listed here.

Abstract

Background: Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats.

Methods: The I/R-related injury was modeled using occlusion and reperfusion of the middle cerebral artery (MCAO/R) in Sprague-Dawley rats. VNS was concurrently applied to the vagus nerve using a stimulation intensity of 1 mA at a fixed frequency of 20 Hz with a 0.4-ms bipolar pulse width. The stimulation duration and inter-train interval were both 3 s. Next, Morris water maze and shuttle-box behavioral experiments were conducted to assess the effects of VNS on the recovery of learning, memory, and inhibitory avoidance following I/R injury. Intracerebroventricular injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a selective neurotoxin for noradrenergic neurons, was used to evaluate the role of norepinephrine (NE) as a mediator of therapeutic effects of VNS on cognitive recovery.

Results: Compared with the MCAO/R group, the VNS+MCAO/R group had improved spatial memory as indicated by swimming path lengths and escape latencies in the Morris water maze, and fear memory, as indicated by the avoidance conditioned response rate, mean shock duration, and avoidance time in shuttle-box behavior experiments. Compared with the VNS+MCAO/R group, the DSP-4+VNS+MCAO/R group, which had reduced NE levels in cortical and hippocampal brain regions, showed a reversal of the VNS-induced benefits on spatial and fear memory performance.

Conclusions: VNS improves spatial and fear memory in a rat model of MCAO/R injury. However, a reduction in NE from the administration of DSP-4 blocks these protective effects, suggesting that NE may contribute to the influence exhibited by VNS on memory performance in rats with cerebral I/R-related injury.

Citing Articles

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.

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A narrative review of vagus nerve stimulation in stroke.

Hu Y, Xiong R, Pan S, Huang K J Cent Nerv Syst Dis. 2024; 16:11795735241303069.

PMID: 39677973 PMC: 11645777. DOI: 10.1177/11795735241303069.

Vagus Nerve Stimulation for Improvement of Vascular Cognitive Impairment.

E R, Wang Y Neuropsychiatr Dis Treat. 2024; 20:1445-1451.

PMID: 39072312 PMC: 11283790. DOI: 10.2147/NDT.S465249.

The protective role of vagus nerve stimulation in ischemia-reperfusion injury.

Zhang Q, Zhang L, Lin G, Luo F Heliyon. 2024; 10(10):e30952.

PMID: 38770302 PMC: 11103530. DOI: 10.1016/j.heliyon.2024.e30952.

Effect of transcranial direct current stimulation combined with transcutaneous auricular vagus nerve stimulation on poststroke cognitive impairment: a study protocol for a randomised controlled trial.

Liu W, Cheng X, Zhang Y, Liao W BMJ Open. 2024; 14(4):e082764.

PMID: 38604630 PMC: 11015246. DOI: 10.1136/bmjopen-2023-082764.

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