Open Access Research

Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats

Stanka Mihaylova1, Anke Killian1, Konstantin Mayer2, Soni Savai Pullamsetti2, Ralph Schermuly3 and Bernhard Rosengarten1*

Author Affiliations

1 Department of Neurology, Justus Liebig University, Klinikstrasse 33, D-35392, Giessen, Germany

2 Department of Internal Medicine, Justus Liebig University, Klinikstrasse 36, D-35392, Giessen, Germany

3 Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, D-61231, Bad Nauheim, Germany

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Journal of Neuroinflammation 2012, 9:183  doi:10.1186/1742-2094-9-183

Published: 25 July 2012

Abstract

Background

In sepsis syndromes the severity of the inflammation triggers microvascular dysfunction and early organ failure. We studied the effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculatory integrity in an endotoxinemic rat model.

Methods

In both control and endotoxinemic (5 mg/kg lipopolysaccharide i.v.) rats, the effect of cervical bilateral vagotomy with or without left-sided distal vagus nerve stimulation were compared to non-vagotomized, nonstimulated group (sham). Neurovascular coupling was analyzed by electrical forepaw stimulation, EEG, and cortical laser-Doppler flow recording. Resting cerebral blood flow, evoked potentials and hemodynamic responses, were obtained over a period of 4.5 hours. Regulation of the nitric oxide system (iNOS expression and nitrite/nitrate measurements), cytokines (IFN-γ, TNF-α, IL-6, IL-10), hypoxic and apoptosis signaling molecules (HIF-2α, Bax) were measured at the end of experiments.

Results

In endotoxinemic rats, vagus nerve stimulation tended to increase anti-inflammatory cytokine levels and resulted in a stabile hemodynamic response (28 ± 13%; versus baseline). Vagotomized animals incurred a pro-inflammatory response (7 ± 4%; P < 0.0001 versus baseline) and produced more HIF-2α than vagotomized vagus nerve stimulated (VNS) animals. Evoked potential amplitudes were stabilized in VNS (15 ± 7 μV; n.s. versus baseline) as compared to vagotomised rats (8 ± 5 μV; P < 0.001 versus baseline). However, no effects were observed on apoptosis markers or nitric oxide levels.

Conclusions

Vagus nerve stimulation in endotoxinemic rats had a positive effect on neurovascular coupling and stabilized evoked potentials.

Keywords:
Microcirculation; Brain; Neurovascular coupling; Evoked potentials; Hypoxia; Sepsis; Inflammation; Lipopolysaccharide; EEG; Vagus nerve stimulation