Blockade of IL-21 signaling before or after tMCAO reduces infarct size in WT mice. (a) Infarct volumes 24 h after tMCAO in WT mice treated with 500 µg recombinant mIL-21R.Fc or PBS 1 h before (pretreatment) or 2 h after (posttreatment) surgery. Representative TTC-stained brain slices shown on left (n = 3–4 mice per group). (b) Still image from Video 1 depicting behavioral differences between WT mice posttreated with IL-21R.Fc or PBS. (c) IL-21R.Fc protein levels in the indicated organs 20–24 h after tMCAO in WT mice injected with 500 µg IL-21R.Fc 2 h after start of reperfusion (n = 2–4 mice per group). N.D., not detected. Data are representative of two independent experiments. **, P < 0.01; ***, P < 0.001, by Student’s t test. Error bars indicate SEM. Representative images of postmortem paraffin-embedded human acute stroke lesions stained with control sera (d), or primary antibodies against CD4 (e and g [ii-iii]), IL-21 (f and g [iii]), or eosin (g [i]) visualized with Fast Red (d, e, and g) and/or DAB (d, f, and g [iii]) and counterstained with hematoxylin. High magnification images are shown on right. Arrows indicate positive staining. Bars, 50 µm.