Modulation of brain immune microenvironment and cellular dynamics in systemic inflammation

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• Sepsis-associated encephalopathy (SAE) affects ~70% of sepsis patients, causing mortality and cognitive issues.
• Limited understanding of SAE development, especially brain microenvironment cellular communication.

Purpose of the Study:

• Investigate myeloid cell impact on brain immune microenvironment via glial alterations.
• Develop tools to analyze neuroinflammation-associated cellular interactions.
• Map dynamic brain immune microenvironment changes during systemic inflammation.

Main Methods:

• Utilized bulk and single-cell transcriptomics from human/mouse sepsis models.
• Developed DeconvCellLink R package for cellular interaction network analysis.
• Constructed dynamic brain immune microenvironment map using time-series data.

Main Results:

• Identified conserved sepsis-associated genes regulating immune signaling, despite model differences.
• Revealed temporal immune cell responses to systemic inflammation via cellular networks and cytokines.
• Demonstrated valproic acid mitigates sepsis-induced neuroinflammation by modulating glial cells.

Conclusions:

• SAE involves innate immune overactivation, with neutrophils playing a key role.
• Dynamic cellular communication networks offer insights into sepsis-induced brain dysfunction.
• Provides a framework for novel therapeutic strategies against SAE.