Vagus nerve stimulation reduces spreading depolarization burden and cortical infarct volume in a rat model of stroke

PLoS One. 2020 Jul 23;15(7):e0236444. doi: 10.1371/journal.pone.0236444. eCollection 2020.

Abstract

Cortical spreading depolarization (SD) waves negatively affect neuronal survival and outcome after ischemic stroke. We here aimed to investigate the effects of vagus nerve stimulation (VNS) on SDs in a rat model of focal ischemia. To this end, we delivered non-invasive VNS (nVNS) or invasive VNS (iVNS) during permanent middle cerebral artery occlusion (MCAO), and found that both interventions significantly reduced the frequency of SDs in the cortical peri-infarct area compared to sham VNS, without affecting relative blood flow changes, blood pressure, heart rate or breathing rate. In separate groups of rats subjected to transient MCAO, we found that cortical stroke volume was reduced 72 h after transient MCAO, whereas stroke volume in the basal ganglia remained unchanged. In rats treated with nVNS, motor outcome was improved 2 days after transient MCAO, but was similar to sham VNS animals 3 days after ischemia. We postulate that VNS may be a safe and efficient intervention to reduce the clinical burden of SD waves in stroke and other conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Disease Models, Animal
  • Heart Rate / physiology
  • Humans
  • Infarction / physiopathology
  • Infarction / therapy*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / therapy
  • Rats
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / therapy
  • Stroke / physiopathology
  • Stroke / therapy*
  • Vagus Nerve Stimulation / adverse effects
  • Vagus Nerve Stimulation / methods*

Grants and funding

This work was supported by grants to GCP from the German Science Foundation DFG (FOR 2795/PE1193/6-1) and the DZNE (DEMDAS Intersite grant). The funder electroCore Inc. provided support in the form of materials (electrodes and stimulators) and salary for author BJS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.