Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke

Area of Science:

• Neuroscience
• Immunology
• Metabolic Biology

Background:

• Neutrophil aggregation and clearance are critical in acute ischemic stroke-induced neuroinflammation.
• Microglial phagocytosis, essential for clearing debris, is significantly influenced by cellular energy metabolism.

Purpose of the Study:

• To investigate the role of Resolvin D1 (RvD1) in modulating microglial function and energy metabolism post-ischemic stroke.
• To determine if RvD1 can enhance microglial phagocytosis of neutrophils and alleviate neuroinflammation.

Main Methods:

• Investigated the effect of RvD1 on microglial phagocytosis of neutrophils in an ischemic stroke model.
• Analyzed RvD1-induced changes in microglial energy metabolism, including glycolysis and oxidative phosphorylation (OXPHOS).
• Examined the role of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in RvD1-mediated metabolic reprogramming.

Main Results:

• RvD1 significantly promoted microglial phagocytosis of neutrophils, reducing neutrophil accumulation in the ischemic brain.
• RvD1 reprogrammed microglial energy metabolism from glycolysis to OXPHOS, enhancing ATP production.
• RvD1-induced metabolic shift was dependent on enhanced glutamine uptake, glutaminolysis, and AMPK activation.

Conclusions:

• RvD1 effectively promotes microglial phagocytosis of neutrophils by reprogramming immunometabolism in ischemic stroke.
• Modulating microglial energy metabolism with RvD1 offers a potential therapeutic strategy for stroke treatment.
• Targeting microglial immunometabolism presents a novel avenue for stroke therapy.