Modulating the Inflammatory Reflex in Rats Using Low-Intensity Focused Ultrasound Stimulation of the Vagus Nerve
Kelsey M. Wasilczuk, Kelsey C. Bayer, Jesse P. Somann, Gabriel O. Albors, Jennifer Sturgis, L. Tiffany Lyle, J. Paul Robinson, Pedro P. Irazoqui
Ultrasound in Medicine & Biology 2019, 45, 481-489 · 10.1016/j.ultrasmedbio.2018.09.005
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, I SPPA = 3 W/cm 2 ). 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.
Abstract via europepmc.
Exposures
Exposure 1: Focused ultrasound vagus nerve stimulation (uVNS)
Target: vagus nerve — “left cervical vagus nerve (surgically exposed)”
Device: Sonic Concepts · Sonic Concepts · H-115 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 4 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 4% | |
| Sonication duration (s) | 300 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 3 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | 1.2 | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Focused ultrasound was delivered for 5 min per stimulation session, applied to the surgically exposed left vagus nerve via a coupling cone and ultrasound gel. Animals received either a single stimulation (u1VNS) or three stimulations (u3VNS, u3Vx) at t=30, 90 and 150 min relative to LPS injection.
Flags from extraction
n_subjects— Paper never states a combined total for ultrasound-exposed animals; group sizes for the three uVNS groups (u1VNS=11, u3VNS=8, u3Vx=4) are listed instead of summed.exposures[0].free_field.isppa_w_cm2— Intensity was measured with a hydrophone in water at the focus but described in the text as the intensity 'applied to the vagus nerve'; since the nerve was surgically exposed and coupled with gel (no skull path), this was treated as a free-field measurement, but the paper does not explicitly state the domain.randomised— Paper does not state whether animals were randomly allocated to groups.