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

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. © 2012 mihaylova et al.; licensee biomed central ltd.