Surgery impairs glymphatic activity and cognitive function in aged mice.
Summary
In vivo two-photon imaging revealed that surgery did not alter glymphatic CSF tracer influx in adult mice but significantly worsened age-related impairment in aged mice at 24 hours, correlating with poorer T-maze performance. The data support glymphatic dysfunction as a mechanistic contributor to postoperative cognitive disturbances in aging.
Key Findings
- In adult mice, CSF tracer influx along periarteriolar pathways was rapid and unaffected by surgery vs sham.
- In aged mice, tracer influx was delayed and further impaired by surgery compared with sham controls.
- Glymphatic impairment after surgery correlated with poorer T-maze performance in aged mice.
Clinical Implications
Motivates perioperative strategies to preserve brain waste clearance in older adults (e.g., optimizing sleep, hemodynamics, ventilation, and sedatives) and supports targeting glymphatic pathways in PND prevention studies.
Why It Matters
Provides mechanistic evidence linking surgery to exacerbated glymphatic dysfunction in aging, a plausible pathway for postoperative delirium and cognitive decline.
Limitations
- Preclinical mouse model; human applicability requires caution.
- Single postoperative timepoint (24 h); sample sizes not specified; potential anesthesia/surgery confounders not fully dissected.
Future Directions
Test perioperative interventions that enhance glymphatic flow in aged subjects and translate imaging/CSF biomarkers to clinical studies of postoperative delirium.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic study in animals providing pathophysiological insight.
- Study Design
- OTHER