Modulating the Inflammatory Reflex in Rats Using Low-Intensity Focused Ultrasound Stimulation of the Vagus Nerve

Ultrasound Med Biol. 2019 Feb;45(2):481-489. doi: 10.1016/j.ultrasmedbio.2018.09.005. Epub 2018 Nov 2.

Abstract

Tumor necrosis factor α (TNF-α) is linked to several chronic inflammatory diseases. Electrical vagus nerve stimulation reduces serum TNF-α levels but may cause chronic nerve damage and requires surgery. Alternatively, we proposed focused ultrasound stimulation of the vagus nerve (uVNS), which can be applied non-invasively. In this study, we induced an inflammatory response in rats using lipopolysaccharides (LPS) and collected blood to analyze the effects of uVNS on cytokine concentrations. We applied one or three 5-min pulsed focused ultrasound stimulation treatments to the vagus nerve (250 kHz, ISPPA = 3 W/cm2). Animals receiving a single ultrasound application had an average reduction in TNF-α levels of 19%, similar to the 16% reduction observed in electrically stimulated animals. With multiple applications, uVNS therapy statistically reduced serum TNF-α levels by 73% compared with control animals without any observed damage to the nerve. These findings suggest that uVNS is a suitable way to attenuate TNF-α levels.

Keywords: Lipopolysaccharides; Low-intensity focused ultrasound; Tumor necrosis factor α; Vagus nerve stimulation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Inflammation / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / physiology*
  • Ultrasonic Waves*
  • Vagus Nerve / physiopathology*
  • Vagus Nerve Stimulation / methods*