title: Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis.
abstract: OBJECTIVE
  Electrical vagus nerve stimulation inhibits proinflammatory cytokine production and prevents shock during lethal systemic inflammation through an alpha7 nicotinic acetylcholine receptor (alpha7nAChR)-dependent pathway to the spleen, termed the cholinergic anti-inflammatory pathway. Pharmacologic alpha7nAChR agonists inhibit production of the critical proinflammatory mediator high mobility group box 1 (HMGB1) and rescue mice from lethal polymicrobial sepsis. Here we developed a method of transcutaneous mechanical vagus nerve stimulation and then investigated whether this therapy can protect mice against sepsis lethality.
  
  
  METHODS
  Prospective, randomized study.
  
  
  METHODS
  Institute-based research laboratory.
  
  
  METHODS
  Male BALB/c mice.
  
  
  METHODS
  Mice received lipopolysaccharide to induce lethal endotoxemia or underwent cecal ligation and puncture to induce polymicrobial sepsis. Mice were then randomized to receive electrical, transcutaneous, or sham vagus nerve stimulation and were followed for survival or euthanized at predetermined time points for cytokine analysis.
  
  
  RESULTS
  Transcutaneous vagus nerve stimulation dose-dependently reduced systemic tumor necrosis factor levels during lethal endotoxemia. Treatment with transcutaneous vagus nerve stimulation inhibited HMGB1 levels and improved survival in mice with polymicrobial sepsis, even when administered 24 hrs after the onset of disease.
  
  
  CONCLUSIONS
  Transcutaneous vagus nerve stimulation is an efficacious treatment for mice with lethal endotoxemia or polymicrobial sepsis.
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors: Jared M
authors: JM
authors: Huston
authors: Margot
authors: M
authors: Gallowitsch-Puerta
authors: Mahendar
authors: M
authors: Ochani
authors: Kanta
authors: K
authors: Ochani
authors: Renqi
authors: R
authors: Yuan
authors: Mauricio
authors: M
authors: Rosas-Ballina
authors: Mala
authors: M
authors: Ashok
authors: Richard S
authors: RS
authors: Goldstein
authors: Sangeeta
authors: S
authors: Chavan
authors: Valentin A
authors: VA
authors: Pavlov
authors: Christine N
authors: CN
authors: Metz
authors: Huan
authors: H
authors: Yang
authors: Christopher J
authors: CJ
authors: Czura
authors: Haichao
authors: H
authors: Wang
authors: Kevin J
authors: KJ
authors: Tracey
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia; D024243:HMGB1 Protein / Q000097:blood*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015213:Neuroimmunomodulation; D011446:Prospective Studies; D011897:Random Allocation; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D016019:Survival Analysis; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D014630:Vagus Nerve
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein