KNG deficiency reduces intracerebral thrombosis and improves cerebral blood flow after stroke. (A) Accumulation of fibrin(ogen) in the infarcted (i) and contralateral (c) cortices and basal ganglia (BG) of wild-type (WT) mice, Kng^−/−mice and Kng^−/− mice reconstituted with human kininogen (KNG) was analyzed by immunoblotting 24 hours after tMCAO (top), and bands were quantified by densitometry (bottom; N = 3-4 per group). One representative immunoblot of each group is shown. AU indicates arbitrary units. (B) Immunohistochemical localization of fibrin(ogen) in the lumina of brain microvessels (stained with the endothelial marker CD31) 24 hours after tMCAO in the infarcted hemispheres of WT mice or Kng^−/− mice. Hoechst staining (blue) depicts cell nuclei. One representative panel per group of 3 independent experiments is shown. Scale bar represents 50 μm. (C left) Representative H&E staining from the infarcted hemispheres of WT mice and Kng^−/− mice on day 1 after tMCAO. Thrombotic vessels were abundant in WT mice (arrows), whereas the microvascular patency was significantly increased in Kng^−/− mice (arrowheads), and this was confirmed by calculation of the thrombosis index (right; N = 5 per group). Scale bar represents 100 μm. (D) Reduced intracerebral thrombosis in Kng^−/− mice improved CBF in the territory of the right middle cerebral artery 12 and 24 hours after reperfusion compared with WT mice as determined by serial laser Doppler flow measurements. No differences in CBF were detectable at baseline (before ischemia), immediately after insertion of the filament (ischemia), or immediately after reperfusion (removal of the filament; N = 8 per group and time point). (A) ***P < .001, *P < .05, 2-way ANOVA, followed by Bonferroni multiple comparison test, group comparisons as indicated in the figure. (C) **P = .005, unpaired Student t test. (D) ***P < .001, **P < .01, 2-way ANOVA, followed by Bonferroni multiple comparison test compared with WT mice.