Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
Yukio Imamura, Hisatake Matsumoto, Jun Imamura, Naoya Matsumoto, Kazuma Yamakawa, Nao Yoshikawa, Yuki Murakami, Satoko Mitani, Junichiro Nakagawa, Tomoki Yamada, Hiroshi Ogura, Jun Oda, Takeshi Shimazu
Frontiers in Neuroscience 2023 · 10.3389/fnins.2023.1211608
Abstract
Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1β (IL-1β) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1β levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1β levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.
Abstract via europepmc.
Exposures
Exposure 1: Ultrasound VNS (bilateral cervical vagus)
Target: vagus nerve — “bilateral cervical vagal nerve (VN) of the mice”
Device: other named manufacturer · ITO · US-731 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓?⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | 50 | ✓✓✓⚑ |
| Sonication duration (s) | 1,200 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 |
Commercial therapy ultrasound applied sequentially to both sides of the neck for 20 min at 3.0 W/cm2 and 50% duty, under deep anaesthesia, at 3 h or 18 h (or 36 h) after LPS.
Flags from extraction
exposures[0].fundamental_frequency_khz— 1 MHz is stated for the ultrasound VNS used to evoke vagal action potentials; the frequency of the US-731 therapy device is not stated. A 300 kHz device was used only for characterisation.exposures[0].unspecified_domain.isppa_w_cm2— Paper gives 'an intensity of 3.0 W/cm2' with no metric (Isppa or Ispta) or domain; left empty.n_subjects— 163 mice were used across all experiments, including non-sonicated controls; 10 died and were excluded.exposures[0].timing.duty_cycle_pct— Duty 50% stated without PRF or pulse duration.blinding— Some experiments used a blinded second experimenter; not all.