The Effect of Anesthesia and Surgery on Postoperative Changes in Plasma biomarkers of neuronal injury, Alzheimer's disease, and inflammation in healthy subjects

Abstract Background: Anesthesia and surgery have been linked to neurological sequelae such as perioperative neurocognitive disorders (PND) and increased risk of Alzheimer's disease (AD). The exact mechanisms of PND remain ambiguous and controversial, which were deserved to explore further. Methods: Healthy subjects undergoing general anesthesia for orthognathic surgery were prospectively randomized to receive propofol or sevoflurane for anesthetic maintenance. Blood samples were taken preoperatively and at 3, 24, and 48 hours after surgery. Neurofilament light (NFL), tau, Amyloid β (Aβ)40, Aβ42 and 21 inflammatory mediators in plasma were measured using highly sensitive assays.Results: A total of 50 healthy subjects were enrolled. The mean (SD) age was 24.80(4.63) years. Plasma NFL increased at each measurement from a baseline mean (SD) of 22.3 (20.4) pg/mL to a maximal mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 599%, at 3 hours postoperatively. NFL level began to decline at 24 hours, but remained higher at 48 hours. The levels of Aβ40 and Aβ42 decreased at 3 hours, and to minimum mean (SD) of 196.70 (38.61) pg/mL and 8.01(1.66) pg/mL at 24 hours postoperatively, respectively. There were no significant differences in the concentrations of plasma tau after anesthesia and surgery. Plasma IL-6, IL-7, IL-8, IL-10, TNF-α, I-TAC and MIP-1β were significantly increased at 3 hours postoperatively and then declined, which had a similar trajectory with a return to baseline. The peak levels of NFL, IL-6, IL-8, TNF-α and MIP-1β correlated with duration of surgery. The peak plasma NFL level significantly correlated with the levels of IL-6 and IL-8.Conclusions: In the healthy adults, general anesthesia and surgery were associated with an increase in NFL, and a decrease in Aβ40 and Aβ42 in the plasma. Elevated plasma NFL levels might be attributed to many of inflammatory mediators. The data indicate systemic inflammation after anesthesia and surgery may induce neuronal injury. These preliminary findings in healthy subjects could help us to understand the effects of anesthesia/surgery on brain and the potential mechanisms of PND.Trial Registration: The study was registered in Chinese Clinical Trial Registry on Feb 11st, 2019 (ChiCTR1900021289).