Ablation of the sphenopalatine ganglion does not attenuate the infarct reducing effect of vagus nerve stimulation

Abstract

Electrical stimulation of the cervical vagus nerve reduces infarct size by approximately 50% after cerebral ischemia in rats. The mechanism of ischemic protection by vagus nerve stimulation (VNS) is not known. In this study, we investigated whether the infarct reducing effect of VNS was mediated by activation of the parasympathetic vasodilator fibers that originate from the sphenopalatine ganglion (SPG) and innervate the anterior cerebral circulation. We examined the effects of electrical stimulation of the cervical vagus nerve in two groups of rats: one with and one without SPG ablation. Electrical stimulation was initiated 30 min after induction of ischemia, and lasted for 1h. Measurement of infarct size 24h later revealed that the volume of ischemic damage was smaller in those animals that received VNS treatment (41.32±2.07% vs. 24.19±2.62% of the contralateral hemispheric volume, n=6 in both; p<0.05). SPG ablation did not abolish this effect; the reduction in infarct volume following VNS was 58% in SPG-damaged animals, 41% in SPG-intact animals (p>0.05). In both SPG-intact and SPG-damaged animals VNS treatment resulted in better motor outcome (p<0.05 vs. corresponding controls for both). Our findings show that VNS can protect the brain against acute ischemic injury, and that this effect is not mediated by SPG projections.

Conflict of interest statement

Conflicts of Interest: The authors report no conflicts of interest.

Copyright © 2012 Elsevier B.V. All rights reserved.

Figures

Figure 1

(A) ABP, HR, and rCBF decreased transiently during electrical stimulation, as seen in the representative recordings. However, VNS had no overall effect on MABP (B), HR (C), and rCBF (D), regardless of SPG ablation. Repeated measures of ANOVA: F(3,20) = 0.008, p=0.99 for MABP, ANOVA: F(3,20) = 0.43, p=0.73 for HR, and F(3,20) = 0.16, p=0.92 for rCBF.

Figure 1

(A) ABP, HR, and rCBF decreased transiently during electrical stimulation, as seen in the representative recordings. However, VNS had no overall effect on MABP (B), HR (C), and rCBF (D), regardless of SPG ablation. Repeated measures of ANOVA: F(3,20) = 0.008, p=0.99 for MABP, ANOVA: F(3,20) = 0.43, p=0.73 for HR, and F(3,20) = 0.16, p=0.92 for rCBF.

Figure 2

The effect of VNS on infarct size (A) and neurological deficit (B) after MCA occlusion. (A) VNS is associated with reduced infarct size in both SPGi and SPGd animals. Among sham stimulation animals, the infarct volume was larger in shamSPGd than shamSPGi. ANOVA F(3,20)=22.04, p<0.0001; Student-Newman-Keuls test: * p<0.05 vs. shamSPGi, +p<0.05 vs. shamSPGd. (B) VNS is associated with better functional outcome in both SPGi and SPGd animals 24 h after ischemia. Repeated measures ANOVA: F(3,20)=6.14, p=0.0039; Mann-Whitney U test: * p<0.05 vs. shamSPGi, +p<0.05 vs. shamSPGd.