title: Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats.
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.
authors: Department of Neurology, Justus Liebig University, Klinikstrasse 33, D-35392, Giessen, Germany.
authors: Stanka
authors: S
authors: Mihaylova
authors: Anke
authors: A
authors: Killian
authors: Konstantin
authors: K
authors: Mayer
authors: Soni Savai
authors: SS
authors: Pullamsetti
authors: Ralph
authors: R
authors: Schermuly
authors: Bernhard
authors: B
authors: Rosengarten
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014630:Vagus Nerve / Q000502:physiology*; D055536:Vagus Nerve Stimulation / Q000379:methods*