The Potential Protective Effect of Mesencephalic Astrocyte-Derived Neurotrophic Factor on Post-Operative Delirium Via Inhibiting Inflammation and Microglia Activation

Background: The increased inflammation is closely correlated with post-operative delirium (POD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effect on inflammatory diseases. However, the relationship between MANF and POD is still undefined. This study aimed to explore the potential effect of MANF on POD.

Methods: Pre- and post-operative levels of MANF and inflammatory cytokines were measured in serum from POD and non-POD patients by ELISA, as well as endogenous MANF in serum from healthy individuals with different ages. Endogenous MANF in mice brain from different ages was also measured. Abdominal surgery was performed for POD mice model. POD-like behavior changes in mice were evaluated using buried food test, open field test and Y maze test.

Results: Endogenous MANF was decreased in age-dependent manner in both humans and mice. The pre-operative level of MANF in serum from POD patients was lower compared with that in non-POD patients (p=0.016). MANF increase in serum after surgery was less in POD patients than that in non-POD patients (p<0.001). In mice, recombinant human MANF reversed the surgery-induced elongation of latency to eat food, increase in latency to center and increase in time in center in open field test, and also increase in duration in novel arm in Y maze test. In addition, MANF inhibited surgery-induced inflammation, microglial activation and M1 polarization in mice.

Conclusion: The relative low MANF level may contribute to POD in the elderly. MANF has a protective role against POD-like behavior changes in mice.