Increasing interleukin-17 induced by β-Amyloid deposition is involved in early cognitive decline after sevoflurane anesthesia.

Postoperative delirium is a major concern in elderly patients and is associated with early cognitive decline after anesthesia exposure. Sevoflurane anesthesia increases amyloid-β (Aβ) production, leading to neuroinflammation, blood-brain barrier (BBB) disruption, and postoperative delirium. Interleukin-17 (IL-17) is implicated in BBB breakdown, and Aβ deposits induce elevated expression. Hence, we explored the relationships between early postoperative cognitive alterations and Aβ deposits, IL-17 expression in the hippocampus, and BBB damage in aged rats after fracture surgery under sevoflurane anesthesia. Aged rats underwent fracture surgery under 3.6% sevoflurane for 2 h. Cognitive changes were assessed using fear conditioning and Y-maze tests, and hippocampal occludin and Ly6g expression were measured using Western blotting. Aβ42, IL-17, and MMP-9 levels were measured using enzyme-linked immunosorbent assays, and BBB disruption was evaluated using Evans Blue at 6, 12, and 24 h post-anesthesia. We intrathecally administered the γ-secretase inhibitor (DAPT) and IL-17 antiserum to inhibit Aβ42 deposition and IL-17 expression, respectively. We observed cognitive changes, hippocampal Aβ42, Ly6g, IL-17, occludin, and MMP-9 levels, and BBB disruption 24 h post-anesthesia. Further, we noticed decreased freezing and residence time in the new Y-maze arm in aged rats, increased Aβ42, IL-17, MMP-9, and Evans blue contents, and decreased occludin expression at 6 h post-anesthesia. These phenotypes worsened at 12 and 24 h. However, DAPT and IL-17 antiserum administration improved cognitive performance and various hippocampal parameters 24 h post-anesthesia. Our study suggests that early postoperative cognitive decline is likely linked to Aβ42 deposition, triggering neuroinflammation and BBB disruption via increased IL-17 expression.