Abstract: TH-PO0125
Abdominal Ultrasonography Activates Vagal Afferents and Induces the Cholinergic Anti-Inflammatory Pathway: Potential Noninvasive Therapy for AKI
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Shimoyama, Kotaro, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Umene, Ryusuke, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Wu, Chia-Hsien, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Nakamura, Yasuna, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
- Inoue, Tsuyoshi, Nagasaki Daigaku Daigakuin Ishiyakugaku Sogo Kenkyuka, Nagasaki, Nagasaki Prefecture, Japan
Background
The cholinergic anti-inflammatory pathway (CAP), activated by vagus nerve stimulation (VNS), suppresses systemic inflammation through α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. While VNS has demonstrated protective effects in preclinical models of acute kidney injury (AKI), its invasive nature limits its clinical utility. Recent studies suggest that abdominal ultrasound (US) may suppress AKI and systemic inflammation in a noninvasive manner, potentially via α7nAChR-dependent mechanisms. However, the neural circuitry involved in US-induced effects remains poorly defined. We hypothesized that abdominal US activates vagal afferent fibers and mimics CAP to exert anti-inflammatory effects.
Methods
Male C57BL/6J mice were administered lipopolysaccharide (LPS, 15 mg/kg, i.p.) to induce sepsis. Abdominal US (burst mode, 10 minutes) was applied both before and after LPS administration. To assess the role of vagal signaling, US effects were evaluated under two conditions: (1) subdiaphragmatic vagotomy and (2) cervical capsaicin application to selectively ablate afferent vagal fibers. Neural activation was assessed via c-Fos immunostaining in the nucleus tractus solitarius (NTS) and electrophysiological recordings of cervical vagus nerve activity during US stimulation. Splenic inflammatory cytokine expression was quantified by real-time PCR. CAP dependency was further evaluated using macrophage-specific α7nAChR knockout mice.
Results
US stimulation significantly reduced plasma TNF-α levels and downregulated inflammatory cytokines in the spleen 1 hour after LPS challenge. These effects were abolished in α7nAChR-deficient macrophage mice, confirming CAP involvement. Additionally, both vagotomy and afferent vagal blockade via capsaicin negated the anti-inflammatory effects of US, highlighting the requirement for vagal afferent signaling. US also increased c-Fos expression in the NTS and enhanced afferent activity in the cervical vagus nerve during stimulation.
Conclusion
Abdominal ultrasound activates vagal afferents and elicits CAP-like anti-inflammatory effects in a sepsis model. This noninvasive neuromodulation strategy offers a promising therapeutic approach for inflammation-related disorders, including AKI.