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Front. Neurol. | doi: 10.3389/fneur.2018.00798

Vagus Nerve Stimulation Attenuates Cerebral Microinfarct and Colitis-induced Cerebral Microinfarct Aggravation in Mice

 Xiaofeng Chen1,  Xiaofei He2, Shijian Luo1, Yukun Feng1, Fengyin Liang2, Taotao Shi1, Ruxun Huang2,  Zhong Pei2* and  Zhendong Li1*
  • 1Department of Neurology, Fifth Affiliated Hospital of Sun Yat-sen University, China
  • 2Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, China

Cerebral cortical microinfarct (CMI) is common in patients with dementia and cognitive decline. Emerging studies reported that intestinal dysfunction influenced the outcome of ischemic stroke and that vagus nerve stimulation (VNS) protected against ischemic stroke. However, the effects of intestinal dysfunction and VNS on CMI are not clear. Therefore, we examined the influence of colitis and VNS on CMI and the mechanisms of VNS attenuating CMI in mice with colitis. CMI was induced using a two-photon laser. Colitis was induced using oral dextran sodium sulfate (DSS). The cervical vagus nerve was stimulated using a constant current. In vivo blood-brain barrier (BBB) permeability was evaluated using two-photon imaging. Infarct volume, microglial and astrocyte activation, oxidative stress and proinflammatory cytokine levels were assessed using immunofluorescent and immunohistochemical staining. The BBB permeability, infarct volume, activation of microglia and astrocytes and oxidative stress increased significantly in mice with colitis and CMI compared to those in mice with CMI. However, these processes were reduced in CMI mice when VNS was performed. Brain lesions in mice with colitis and CMI were significantly ameliorated when VNS was performed during the acute phase of colitis. Our study demonstrated that VNS alleviated CMI and this neuroprotection was associated with the suppression of BBB permeability, neuroinflammation and oxidative stress. Also, our results indicated that VNS reduced colitis-induced microstroke aggravation.

Keywords: Cerebral microinfarct, Colitis, Vagus Nerve Stimulation, Blood-Brain Barrier, Inflammation, Oxidative Stress

Received: 28 Apr 2018; Accepted: 04 Sep 2018.

Edited by:

Emmanuel Pinteaux, University of Manchester, United Kingdom

Reviewed by:

Adam Denes, Laboratory of Neuroimmunology, Institute of Experimental Medicine, Institute of Experimental Medicine (MTA), Hungary
Frank C Barone, SUNY Downstate Medical Center, United States  

Copyright: © 2018 Chen, He, Luo, Feng, Liang, Shi, Huang, Pei and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD, PhD. Zhong Pei, Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China, peizhong@mail.sysu.edu.cn
MD. Zhendong Li, Fifth Affiliated Hospital of Sun Yat-sen University, Department of Neurology, Zhuhai, China, lizdsysu@163.com