Effects of propofol and surgery on neuropathology and cognition in the 3xTgAD Alzheimer transgenic mouse model

Background. Previous work suggests that anaesthesia and surgery amplify the pathology and cognitive impairment of animals made vulnerable via age or specific transgenes. We hypothesized that surgery under propofol anaesthesia, a widely used i.v. general anaesthetic, has minimal delayed cognitive and neuroinflammatory sequelae in a vulnerable mouse transgenic model. Methods. We conducted caecal ligation and excision surgery in cognitively presymptomatic (11-month-old) 3xTgAD mice under i.p. propofol anaesthesia. Age-matched 3xTgAD control mice received vehicle or propofol without surgery. Morris water maze testing was conducted 3 and 15 weeks later. Brains were examined with quantitative immunohistochemistry for amyloid beta plaques, tau pathology, and microglial activation. Acute changes in neuroinflammatory cytokines were assessed in separate cohorts at 6h. Results. We detected no significant differences between groups in escape latencies at either 3 or 15 weeks, but detected a significant effect of surgery in the probe test at both 3 and 15 weeks. Spatial working memory was unaffected at 16 weeks in any group. No effects of either propofol alone or propofol with surgery were detected on plaque formation, tau aggregates, or neuroinflammation. Acute biochemical assays detected no effects in brain interleukin-10 or interleukin-6 concentrations. Conclusions. Surgery in a vulnerable transgenic mouse under propofol anaesthesia was associated with minimal to no changes in short-and long-term behaviour and no changes in neuropathology. This suggests that propofol anaesthesia is associated with better cognitive outcomes in the aged, vulnerable brain compared with inhalation anaesthesia.