(a) Representative images of the dorsal surface and (b) the ratio of surface hematoma area to hemisphere area of brains at 48 h after intracerebral injection of autologous blood into the right hemisphere or sham injection into the left hemisphere from NDM (n = 15) and DM rats (n = 11). Scale bar, 2 mm. (c) Representative images and the ratio of surface hematoma area to hemisphere area of brains from DM Akita mice (Ins2^Akita, n = 10) and the NDM littermate WT controls (n = 9) following PBS injection into left hemisphere and autologous blood injection into right hemisphere. Scale bar, 2 mm. (d) The ratio of surface hematoma area to hemisphere area of brains at 48 h after intracerebral injection of autologous blood to NDM rats systemically treated with vehicle (Veh, n = 4) or ASP-440 (440, n = 6), and to DM rats systemically treated with vehicle (n = 7), ASP-440 (n = 11), Hoe-140 (Hoe, n = 8), or [des-Arg¹⁰]-Hoe140 (Des-Hoe, n = 5). (e) The ratio of surface hematoma area to hemisphere area of brains at 48 h after intracerebral injection of autologous blood mixed with PK-specific antibody into the right hemisphere or IgG into the left hemisphere of DM rats (n = 6). (f) Representative images of the coronal slices of brains at 2 h after intracerebral injection of blood into the right hemisphere or PBS injection into the left hemisphere from diabetic Klkb1^+/+ and Klkb1^−/−, mice. Scale bar, 2 mm. (g) Hemoglobin content of hemispheres subjected to autologous blood from Klkb1^+/+ (n = 16), Klkb1^+/− (n = 10) and Klkb1^−/− (n = 23) mice. (h) aPTT from Klkb1^+/+, Klkb1^+/−, and Klkb1^−/− mice (n = 6). * P < 0.05; ** P < 0.01; *** P < 0.001.

(a) Effect of PK on collagen-stimulated platelet aggregation. (b) Effect of PK on thrombin or ADP-induced platelet aggregation. (c) Effect of glucose on PK-induced inhibition of collagen-stimulated platelet aggregation. (d) Effects of PK (160 nM), prekallikrein (160 nM) and deactivated PK (De-PK, 160 nM) on collagen-induced platelet aggregation. n = 4 independent experiments. (e) Hemoglobin content of hemisphere and (f) the ratio of hematoma area to hemisphere area of brains from C57BL/6 WT mice subjected to JAQ or rat IgG injection in the contralateral hemisphere (n = 6); C57BL/6 WT mice subjected to PBS injection (n = 10); and FcR γ-chain-deficiency (Fcer1g^−/−) mice subjected to PBS injection (n = 5). (g) Effect of convulxin on PK-induced hematoma expansion in DM rats. n = 6–19 rats. (h) Effects of PK (160 nM) and glucose (Glu, 25 mM) on CRP or convulxin-induced platelet aggregation. n = 3–5 independent experiments. Platelet aggregation was measured by platelet aggregometer for (a–c) and by microplate reader for (d, h). * P < 0.05; ** P < 0.01; *** P < 0.001.

(a) Representative images of the dorsal surface and coronal slice and (b) the ratio of surface hematoma area to hemisphere area of brains at 48 h after intracerebral injection of PK into the right hemisphere or PBS injection into the left hemisphere from NDM (n = 5) and DM rats (n = 7). Scale bar, 2 mm. (c) Hemoglobin and (d) carbonic anhydrase 1 (CA-1) levels in the 5 mm anterior transverse section hemispheres encompassing the injection site. n = 3–7 rats. (e) Time course of hematoma expansion after intracerebral injection of PK into right hemisphere or PBS injection into left hemisphere of DM rats. n = 7–8 rats. (f) Effect of insulin treatment on hematoma expansion following intracerebral PK injection in DM rats. n = 8–12 rats. (g) Time course of blood glucose level after intraperitoneal injection of saline (n = 11) or glucose (n = 15) in rats. (h) The ratio of hematoma area to hemisphere area of brains at 0.5 h following intracerebral PK or PBS injections from saline (n = 10) or glucose intraperitoneal injected rats (n = 13). (i) The ratio of surface hematoma area to hemisphere area of brains from NDM (n = 8) and DM rats (n = 6) at 0.5 h after intracerebral injection of PK or deactivated PK (De-PK). n = 6–14 rats. * P < 0.05; ** P < 0.01; *** P < 0.001.

Sensorgram of the interaction of PK with immobilized collagen type I in the (a) absence or (b) presence of glucose. (c) Effect of glucose on PK binding to aorta tissue. n = 5 pieces rat aorta tissue. (d) Effects of hyperosmotic mannitol or NaCl on PK-induced inhibition of collagen-stimulated platelet aggregation. n = 3 independent experiments. (e) Representative images and (f) the ratio of surface hematoma area to hemisphere area of the dorsal surface of brains at 2 h after intracerebral injection of PK or autologous blood into the right hemisphere or PBS injection into the left hemisphere of mannitol-treated NDM rats (n = 6). * P < 0.05; ** P < 0.01. Scale bar, 2 mm.