Secukinumab ameliorates postoperative cognitive dysfunction in aged mice by reducing meningeal aggregation of γδT cell

Background: It has been found that γδ T-cell aggregation in the meninges is significantly increased after brain injury, which is closely related to the decline in cognitive function. Objective: In this study, we attempted to evaluate the effects of secukinumab (Sck) treatment on postoperative cognitive dysfunction (POCD), γδT cell aggregation, and neuroinflammation in aged mice. Under anesthesia, partial hepatectomy was performed to establish a POCD mouse model, and then Sck was injected subcutaneously. Morris water maze training test was introduced to evaluate the spatial memory ability of mice. ELISA, RT-PCR, immunohistochemistry, Evans blue fluorescent staining, flow cytometry, and Western blotting were introduced to detect cerebral neuroinflammation, microglia activation, blood–brain barrier, and the proportion of γδT cells in POCD mice. The effects of Sck on cognitive function in POCD mice were further analyzed after γδT cell depletion by introduction of anti-TCRγδ antibody (anti-TCRγδ Ab). Results: After subcutaneous injection of Sck, POCD mice showed improved spatial memory capacity, suppressed neuroinflammation in the brain caused by microglia activation, repaired BBB disruption, and reduced proportion of γδT cells. However, there was no significant change in cognitive function in POCD mice after Sck subcutaneous injection based on the introduction of anti-TCR γδ Ab, which may be due to the lack of Sck targeting as a result of γδ T-cell depletion. Conclusion: This study has revealed Sck, a drug that can improve the neuroinflammation and cognitive dysfunction caused by POCD through targeted loss of γδT cells and interfering with the release of inflammatory cytokines.