Dysregulated neural coding in the vagus nerve during long sepsis

Area of Science:

• Neuroscience
• Immunology
• Critical Care Medicine

Background:

• Sepsis is a life-threatening organ dysfunction due to dysregulated host response to infection.
• Long sepsis (LS) describes persistent sequelae in survivors, including cognitive, immune, and cardiovascular issues.
• The vagus nerve, integral to the inflammatory reflex, is implicated in sepsis pathophysiology.

Purpose of the Study:

• To investigate the role of the vagus nerve in a mouse model of long sepsis (LS).
• To characterize vagal nerve activity and its response to inflammatory stimuli in LS.

Main Methods:

• Cecal ligation and puncture (CLP) or sham surgery in male mice.
• Electrophysiological recordings of cervical vagus nerve activity six weeks post-surgery.
• Systemic administration of tumor necrosis factor (TNF) and interleukin-1β (IL-1β) with subsequent vagal response analysis.
• Naïve Bayes decoder used to assess neural code disruption.

Main Results:

• LS mice exhibited significantly higher baseline vagal nerve activity compared to controls.
• LS mice showed dysregulated vagal responses to TNF and IL-1β, with some units decreasing activity.
• Vagal nerve activity patterns in LS mice were significantly altered, indicating disrupted neural coding.

Conclusions:

• Long sepsis fundamentally alters vagus nerve function, characterized by elevated baseline activity and diminished responsiveness to inflammatory signals.
• Neurophysiological dysregulation of the vagus nerve may contribute to persistent multi-organ dysfunction in LS survivors.
• Vagal nerve signaling represents a potential therapeutic target for improving sepsis outcomes.