Surgical Trauma in Mice Modifies the Content of Circulating Extracellular Vesicles

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Surgical procedures induce systemic responses affecting distant organs, including the brain.
• Previous work demonstrated orthopedic surgery causes hippocampal changes linked to cognitive deficits.
• The specific signaling mechanisms for periphery-to-brain communication post-surgery are not well understood.

Purpose of the Study:

• To investigate extracellular vesicles (EVs) as mediators of communication from surgical injury sites to the brain.
• To determine if the molecular cargo of circulating EVs changes quantitatively after surgery.
• To explore if these cargo changes could induce phenotypic modifications in target tissues.

Main Methods:

• Isolation of EVs from mouse serum at 6, 24, and 72 hours post-tibia surgery.
• Proteomic analysis using mass spectrometry to identify protein cargo.
• miRNAomic analysis using RNA-sequencing to profile microRNA cargo.

Main Results:

• Significant differential expression of proteins and microRNAs in circulating EVs detected as early as 6 hours post-surgery, peaking at 24 hours.
• Up-regulation of alpha-synuclein, a protein associated with neurodegenerative diseases, observed at 24 hours post-surgery.
• Analysis suggests post-surgery EVs can modify extracellular matrix and regulate metabolic pathways, including fatty acid metabolism.

Conclusions:

• Surgical interventions significantly alter the molecular cargo of circulating EVs.
• EVs are proposed as potential systemic carriers transmitting remote effects of surgery to the brain.
• Findings highlight EVs as a novel mechanism linking peripheral injury to central nervous system responses.