Reprogramming microglia in sepsis-associated encephalopathy: from pathological dysfunction to therapeutic restoration

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Microglia, the CNS immune cells, are crucial in health and disease.
• In sepsis-associated encephalopathy (SAE), microglia may transition from neuroprotective to neurotoxic phenotypes.
• The precise mechanisms driving this microglial dysfunction in SAE are not fully understood.

Purpose of the Study:

• To propose a framework for understanding microglial reprogramming in SAE.
• To integrate multi-omics, genetics, and imaging data to characterize SAE-associated microglial states.
• To identify therapeutic strategies for restoring protective microglial function.

Main Methods:

• Review integrating single-cell multi-omics, functional genetics, and in vivo imaging.
• Analysis of molecular characteristics and functional alterations (e.g., synaptic pruning) of microglia in SAE.
• Discussion of inflammatory signaling, epigenetic, and metabolic factors.

Main Results:

• Microglial dysfunction in SAE involves complex molecular and functional changes.
• Inflammatory signals, transcriptional/epigenetic networks, and metabolic shifts are key drivers.
• Plasticity of microglia allows for potential therapeutic modulation.

Conclusions:

• Understanding microglial reprogramming in SAE is key to developing targeted therapies.
• Multi-level strategies including epigenetic, metabolic, and gene-editing approaches show promise.
• This mechanistic insight can guide interventions for various neuroinflammatory disorders.