Liver-brain axis mechanism underlying central immune remodeling triggered by peripheral hepatic damage

Area of Science:

• Neuroscience
• Hepatology
• Immunology

Background:

• Liver dysfunction significantly impacts the central nervous system (CNS), leading to neuropsychiatric abnormalities via the liver-brain axis.
• Disruption of this bidirectional network involves neural, immune, and gut microbiota pathways, contributing to CNS injury in liver disease.

Purpose of the Study:

• To review the pathogenesis of neuropsychiatric complications associated with liver dysfunction and transplantation.
• To elucidate the mechanisms of CNS injury, focusing on the liver-brain axis, blood-brain barrier integrity, and neuroinflammation.

Main Methods:

• Comprehensive review of existing literature on liver-brain axis pathophysiology.
• Analysis of molecular pathways, including the TRPM2-SYK-NF-κB pathway in microglia.
• Examination of the role of gut microbiota, immune activation, and barrier functions.

Main Results:

• Toxic metabolites like bilirubin activate microglial pathways, causing neuroinflammation and neural damage in the anterior cingulate cortex.
• Key factors include blood-brain barrier disruption, systemic immune responses, neurotransmitter imbalances, and altered immune cell phenotypes.
• Gut-liver-brain axis crosstalk, meningeal immunity, and circadian rhythm disturbances are critical.

Conclusions:

• Identifies diagnostic biomarkers such as bilirubin and FGF21.
• Proposes therapeutic targets including the TRPM2-SYK-NF-κB pathway, microglial modulation, and gut microbiota interventions.
• Provides a framework for diagnosing and treating liver disease-related neuropsychiatric complications.