NF-κB is central to the relationship between UA and cognitive dysfunction. NF-κB is central to the relationship between UA and cognitive dysfunction. The tests were performed in C57BL/6 mice with stereotactic injection of normal saline or UA (600 ng/ml, 0.6 μl/min, 2 μl), with or without injection of BAY11-7085 (500 nm, 0.6 μl/min, 2 μl) 30 min before UA administration for 21 consecutive days (n = 6 mice per group). A, B, Spatial learning of the mice with stereotactic injection of normal saline or UA (600 ng/ml, 0.6 μl/min, 2 μl), with or without injection of BAY11-7085 (500 nm, 0.6 μl/min, 2 μl) 30 min before UA administration for 21 d, was assessed by a Morris water maze. Each trial was presented as the average of four individual tests, and four trials were performed with escape latency to the platform being recorded in a Morris water maze (Student's t tests, *p < 0.05; **p < 0.01, n = 6 rats per group). C, Expression levels of inflammatory mediators, including proinflammatory cytokines (Il6, Il1b, Tnfa, Socs3, and Ccl2) and TLR4/NF-κB signaling (Tlr4, Nfkbia, Ikbkb, and Ikbke), were determined by qRT-PCR in the hippocampi of the mice injected with saline, BAY11-7085 (500 nm, 2 μl), UA (600 ng/ml, 2 μl), or BAY11-7085 (500 nm, 2 μl) + UA (600 ng/ml, 2 μl) for 21 d (Student's t tests, *p < 0.05; **p < 0.01; ***p < 0.001, n = 6 rats per group). D, Hippocampal tissues was immunostained for GFAP and RelA, Iba-1 and RelA, and NeuN and RelA (400×) 21 d after being injected with saline, BAY11-7085 (500 nm, 2 μl), UA (600 ng/ml, 2 μl), or BAY11-7085 (500 nm, 2 μl) + UA (600 ng/ml, 2 μl). RelA was used for reporting on NF-κB. DAPI nuclear staining revealed all cells in the section. GFAP, DAPI, Merge (DAPI + NF-κB), GFAP + NF-κB; Iba-1, DAPI, Merge (DAPI + NF-κB), Iba-1 + NF-κB; and NeuN, DAPI, Merge (DAPI + NF-κB), and NeuN + NF-κB. All displayed values are the mean ± SEM. Xiaoni Shao et al. J. Neurosci. 2016;36:10990-11005 ©2016 by Society for Neuroscience