IL-21 is up-regulated early in mouse brain, and IL-21–deficient mice are protected after tMCAO. GeArray S Series Mouse Autoimmune and Inflammatory Response gene array of transcripts expressed in pooled brain tissues 24 h after tMCAO or sham procedure (n = 3–6 mice per group). (a) Bar graphs show PCR array spot intensity of genes with a greater than sixfold difference in gene expression in tMCAO compared with sham, normalized to the interquartile mean spot intensity. (b) IL-21 mRNA expression level in ipsilateral hemisphere relative to contralateral hemisphere 24 h after tMCAO (n = 3 per group). Mann-Whitney rank sum test *, P < 0.05. Plots show median, lower, and upper quartile (box) and range (error bars). Infarct volumes of WT and IL-21 KO mice 24 h after tMCAO (c) and 7 d after tMCAO (d). Representative images of TTC-stained 2-mm brain slices shown below (n = 5–7 mice per group). WT and IL-21 KO mice grip strength (e) and Bederson score (f) at 1, 4, and 7 d after 1 h tMCAO (n = 7–8 for each group). (g) Brain vasculature of C57BL/6 and IL-21KO mice perfused transcardially with carbon lampblack (C198-500; Thermo Fisher Scientific) in 20% gelatin ddH₂O. Arrows indicate anterior cerebral (ACA), MCA, posterior cerebral (PCA), basilar (BA), and vertebral arteries (VA), showing point of occlusion (white circle). High magnification images demonstrate no difference in patency of the posterior communicating artery (PComA, arrows). (h) Heart rate and blood pressure of WT and IL-21 KO mice before and after tMCAO (n = 3–4 mice per group). Data are representative of 2–3 independent experiments. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by Student’s t test (single comparison) or one-way ANOVA (multiple comparisons). Error bars indicate SD.