Dexmedetomidine reverses surgery-induced cognitive decline (A) and peripheral (B) and neuroinflammation (C). Three groups of randomly assigned mice (n = 15/group) were treated with (1) vehicle, (2) tibia fracture during anesthesia (Sx/Anesth) + vehicle, and (3) Sx/Anesth + dexmedetomidine before training in the trace fear conditioning paradigm (A). Testing for freezing behavior in the trace fear conditioning context was undertaken 72 h later. Freezing time data are expressed as means ± SD and were analyzed by one-way ANOVA and Tukey post hoc test. Three groups of randomly assigned mice (n = 6/group) were treated with (1) vehicle, (2) tibia fracture during anesthesia (Sx/Anesth) + vehicle, and (3) Sx/Anesth + dexmedetomidine. Mice were euthanized at 24 h, and blood and brain were harvested. Plasma interleukin (IL)-6 was assayed by enzyme-linked immunosorbent assay (B), and hippocampal IL-6 was assayed by quantitative polymerase chain reaction (C). The means ± SD of the mean for expression of IL-6 protein (B) and mRNA (C) were analyzed by one-way ANOVA and Tukey post hoc test. #P < 0.05; *P < 0.01; **P < 0.0001.