Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming.

Area of Science:

• Neuroscience
• Immunology
• Nanotechnology

Background:

• Microglia are key immune cells in the brain and therapeutic targets for neurodegenerative diseases like Parkinson's disease.
• Perfluorocarbon nanodroplets offer oxygen transport and anti-inflammatory benefits, but their role in neuroinflammation is unclear.

Purpose of the Study:

• To investigate the potential of perfluoropentane-based oxygen-loaded nanodroplets (PFP-OLNDs) in modulating microglia-mediated neuroinflammation.
• To explore the therapeutic efficacy of PFP-OLNDs in Parkinson's disease models.

Main Methods:

• Development of perfluoropentane-based oxygen-loaded nanodroplets (PFP-OLNDs).
• In vitro and in vivo assessment of PFP-OLNDs' effects on lipopolysaccharide-induced microglial activation.
• Analysis of microglial metabolic reprogramming and the AKT-mTOR-HIF-1α pathway using ultrahigh-performance liquid chromatography-tandem mass spectrometry.

Main Results:

• PFP-OLNDs pretreatment suppressed M1-type microglia activation in vitro and in vivo, including in a Parkinson's disease mouse model.
• Suppression of microglial activation reduced inflammation, oxidative stress, and cell migration, mitigating neurotoxic effects and neuronal degeneration.
• PFP-OLNDs' anti-inflammatory effects were attributed to the modulation of microglial metabolic reprogramming via the AKT-mTOR-HIF-1α pathway.

Conclusions:

• Novel PFP-OLNDs effectively alleviate microglia-mediated neuroinflammation.
• PFP-OLNDs demonstrate therapeutic potential for neurodegenerative diseases by reprogramming microglial metabolism.
• Targeting microglial metabolic reprogramming represents a promising strategy for treating central nervous system inflammatory conditions.