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

Abstract

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 P 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