Abstract: FR-PO0198
Timing-Dependent Effects of Vagus Nerve Stimulation on Inflammation and Physiology in Sepsis
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Washimine, Norito, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Umene, Ryusuke, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Wu, Chia-Hsien, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Nakamura, Yasuna, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Matsuo, Sayumi, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Nishino, Tomoya, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Inoue, Tsuyoshi, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Background
Sepsis often leads to sepsis-associated acute kidney injury, and multiple interventions have been studied. The autonomic nervous system regulates inflammation via immune cells, a mechanism known as the neuro-immune system. The cholinergic anti-inflammatory pathway (CAP), activated by vagus nerve stimulation (VNS) through α7 nicotinic acetylcholine receptors (α7nAChR) on splenic macrophages, is well studied. Although VNS administered during sepsis induction has shown anti-inflammatory effects, it remains unclear whether stimulation before or after induction alone is sufficient to modulate inflammation. Clarifying the timing and effectiveness of VNS could support the development of neuro-immune-based therapies for sepsis. This study aimed to compare the anti-inflammatory and physiological effects of VNS administered before versus after sepsis induction.
Methods
We established a sepsis model in male C57BL/6 mice (8–15 weeks old) by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). VNS was performed for 10 minutes either 1 hour before or 1 hour after LPS administration. We measured plasma TNF-α levels to evaluate inflammatory responses. Blood pressure was measured noninvasively using the tail-cuff method before and after LPS injection. In addition, we evaluated organ damage markers (e.g., platelet count, creatinine, total bilirubin), acid-base status (pH, bicarbonate), and lactate levels from blood samples.
Results
In septic mice, VNS administered before LPS injection significantly reduced plasma TNF-α levels compared to the LPS and VNS-sham group. In contrast, VNS administered after LPS injection showed no significant reduction and tended to increase TNF-α levels. Although LPS significantly lowered systolic blood pressure, VNS performed after LPS injection did not worsen hypotension. However, lactate acidosis was significantly exacerbated in the post-induction VNS group.
Conclusion
Preventive VNS before sepsis induction exerted anti-inflammatory effects, whereas therapeutic VNS after induction failed to produce similar benefits. These findings suggest that the efficacy of CAP is timing-dependent and may be compromised in the context of peripheral circulatory failure. Understanding how such failure impairs CAP responsiveness may aid the development of CAP-targeted therapies for sepsis.