Effect of vagus nerve stimulation during transient focal cerebral ischemia on chronic outcome in rats
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Updated: May 24, 2026

Preparation of Peripheral Nerve Stimulation Electrodes for Chronic Implantation in Rats
Published on: July 14, 2020
Teruyuki Hiraki1, Wesley Baker, Joel H Greenberg
1Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104-6063, USA.
Abstract:
The aim of this study was to investigate the effect of vagus nerve stimulation (VNS) on infarct volume and neurological recovery up to 3 weeks following transient focal cerebral ischemia. Transient ischemia was produced by filament occlusion of the proximal middle cerebral artery (MCA) in rats. The right vagus nerve was stimulated starting 30 min after MCA occlusion and consisted of 30-sec pulse trains (20 Hz) delivered to the animal's right vagus nerve every 5 min for a total period of 60 min (n = 10). All the procedures were duplicated, but no stimulus was delivered, in a control group (n = 10). Neurological evaluations were performed in all animals at 24 hr, 48 hr, 1 week, 2 weeks, and 3 weeks after MCA occlusion; animals were euthanized; and neuronal damage was evaluated in hematoxylin-eosin-stained sections. The ischemic lesion volume was smaller in the VNS-treated animals in comparison with the nonstimulated group (P < 0.02). Although the functional score in both treated and untreated groups improved over the 3-week observation period (P < 0.001), there was still a statistically significant improvement reszulting from VNS treatment compared with control animals (P < 0.05). Cerebral blood flow changes in the MCA territory during ischemia did not differ between the VNS-treated animals (31.9% ± 10.4% of baseline) and control animals (29.9% ± 9.1%; P = 0.6). Stimulation of the vagus nerve for only a brief period early in ischemia provides neuroprotection in transient ischemia, with neuroprotection persisting for at least 3 weeks.
Insights
Vagus nerve stimulation (VNS) reduces brain infarct volume and improves neurological recovery in rats after transient cerebral ischemia. This neuroprotection persists for at least three weeks, offering a promising therapeutic avenue.
Area of Science:
- Neuroscience
- Neurology
- Ischemic Stroke Research
Background:
- Transient focal cerebral ischemia is a major cause of neurological deficits.
- Current treatments for ischemic stroke have limitations, necessitating novel therapeutic strategies.
- Vagus nerve stimulation (VNS) has emerged as a potential neuroprotective intervention.
Purpose of the Study:
- To investigate the neuroprotective effects of VNS on infarct volume.
- To evaluate the impact of VNS on neurological recovery following transient cerebral ischemia.
- To determine the duration of VNS-induced neuroprotection.
Main Methods:
- Transient focal cerebral ischemia was induced in rats via middle cerebral artery (MCA) occlusion.
- VNS was applied starting 30 minutes after MCA occlusion for 60 minutes.
- Neurological function and infarct volume were assessed at multiple time points up to 3 weeks post-ischemia.
Main Results:
- VNS significantly reduced ischemic lesion volume compared to the control group (P < 0.02).
- VNS treatment led to statistically significant improvements in neurological functional scores (P < 0.05).
- Cerebral blood flow changes during ischemia did not differ between VNS-treated and control groups.
Conclusions:
- Early and brief VNS provides significant neuroprotection in transient focal cerebral ischemia.
- The neuroprotective effects of VNS are sustained for at least 3 weeks.
- VNS represents a promising therapeutic strategy for managing ischemic stroke.
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