LXA4 attenuates perioperative neurocognitive disorders by suppressing neuroinflammation and oxidative stress

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Perioperative neurocognitive disorder (PND) is a common complication in elderly surgical patients, linked to neuroinflammation and microglia activation.
• Lipoxin A4 (LXA4), a lipid mediator, exhibits known anti-inflammatory properties.
• Understanding LXA4's role in PND is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the protective effects of LXA4 against surgery-induced cognitive deficits.
• To explore the underlying mechanisms of LXA4's action in the context of neuroinflammation and microglial activation.

Main Methods:

• An animal model of PND was established using mice subjected to laparotomy under sevoflurane anesthesia.
• LXA4 was administered intraperitoneally prior to surgery.
• BV2 microglial cells were used to study LXA4's effects on M1/M2 polarization, cytokine production, oxidative stress markers, and the SIRT1/NF-κB pathway.

Main Results:

• LXA4 significantly alleviated cognitive impairments and reduced hippocampal neuroinflammation and microglial activation in the PND model.
• In vitro, LXA4 inhibited M1 microglia polarization, promoted M2 polarization, and modulated pro- and anti-inflammatory cytokine levels.
• LXA4 attenuated oxidative stress markers (ROS, NOX2, HO-1) and enhanced antioxidant activity (SOD1, SOD), effects mediated by SIRT1 activation and NF-κB inhibition.

Conclusions:

• LXA4 demonstrates significant neuroprotective effects against surgery-induced cognitive deficits and neuroinflammation.
• The therapeutic potential of LXA4 in PND is likely mediated through the SIRT1/NF-κB signaling pathway in microglia.
• LXA4 represents a promising therapeutic candidate for mitigating neuroinflammation, oxidative stress, and cognitive dysfunction associated with PND.