Dysfunction of inflammation-resolving pathways is associated with postoperative cognitive decline in elderly mice

Postoperative cognitive dysfunction (POCD) refers to a reversible, perioperative mental disorder. POCD increases the likelihood of postoperative complications and the risk for postoperative mortality, typically among elderly patients (age 65 or older). The importance of the cholinergic anti-inflammatory pathway (CAP) in resolving neuro-inflammatory and cognitive decline caused by sterile trauma has been recognized. We speculate that the POCD in elderly mice is associated with dysfunction of CAP.

Mice were assigned to several groups (n = 5 in each group): AM (adult mice) Sham, AM (adult mice) Surgery, EM (elderly mice) Sham, EM (elderly mice) Surgery, and EMP (elderly mice with PNU) Surgery. At 24 h after surgery, assessed the cognitive levels. Pro-inflammatory cytokines in peripheral blood and splenic monocytes (TNF-α, IL-6 and IL-10) were assessed by ELISA and qPCR. Levels of M2 macrophages in hippocampus were visualized by immunofluorescence. Detecting CD11b/c⁺α7 nAChR⁺ cells in the spleens with flow cytometry.

At postoperative 24 h, elderly mice exhibited significantly increased POCD compared with adult mice. The proinflammatory factor TNF-α and IL-6 were higher among elderly surgery mice (EM) compared with adult surgery (AM) and elderly-P surgery mice (EM-P); the anti-inflammatory factor IL-10 and M2 macrophages were lower among EM surgery mice compared with AM surgery and EM-P surgery mice. The CD11b/c⁺α7 nAChR⁺ population of splenocytes was reduced in the EM surgery mice.

The exaggerated and persistent cognitive decline and inflammatory response among elderly mice were associated with dysfunction of CAP, and these phenomena were reversed by α7nAch receptor agonists.