Figure 2
Figure 2. Levels of L5 and LOX-1, L5’s receptor, regulate infarct volume after ischemic stroke in mice. (A) Representative TTC stains of a coronal section of brain tissue for 1 mouse per group at 24 hours after focal cerebral ischemia (top) and the quantification of corresponding brain infarct volumes (bottom) in WT mice treated with PBS, L5 (5 mg/kg), or L1 (5 mg/kg) for 60 minutes before MCAO in addition to TS58 (1 mg/kg, a LOX-1 neutralizing antibody) 110 minutes after MCAO, or in LOX-1−/− mice treated with L5 or PBS. Data are presented as the mean ± SD (n = 8). **P < .01 vs PBS control; ###P < .001 vs L5-treated WT mice. (B) TS58 treatment improved performance in the tape removal test after ischemic stroke. The time needed to remove tape from both the contralateral and ipsilateral paws was recorded for sham-operated mice, WT mice that were treated either with PBS or L5 for 60 minutes before undergoing MCAO and reperfusion, and WT mice treated with L5 (5 mg/kg) for 60 minutes before MCAO and then treated with TS58 (1 mg/kg) 10 minutes before reperfusion. Data are presented as the mean ± SD (n = 8). ***P < .001 vs sham control; ###P < .001 vs L5-treated WT mice. (C) LOX-1 neutralizing antibody inhibits the L5-induced shortening of occlusion times for inducing thrombus formation in mesenteric venules of mice. Mice (WT and LOX-1−/−) were administered isovolumetric PBS solution, L5 (5 mg/kg), or TS58 (1 mg/kg) + L5 (5 mg/kg), and then mesenteric venules were selected for irradiation to induce microthrombus formation. (a) WT mice treated with PBS; (b) WT mice treated with L5; (c) WT mice treated with TS58 and L5; (d) LOX-1−/− mice treated with L5; (e) LOX-1−/− mice treated with PBS. Microscopic images (×400) obtained during the 143-second time period after the injection of fluorescent sodium (15 μg/kg) and transillumination in mice treated with PBS, L5 (5 mg/kg), or TS58 (1 mg/kg) + L5 (5 mg/kg). Arrows indicate platelet plug formation. Photographs are representative of 8 similar experiments. Bar, 30 μm. Data in the bar graph are presented as the mean ± SD (n = 8). ***P < .001 vs PBS control; ##P < .01 vs L5-treated WT mice. (D) TS58 treatment prolongs tail-bleeding time in L5-treated mice. Tail-bleeding time was determined after treatment with PBS or L5 (5 mg/kg) in LOX-1−/− mice and after treatment with PBS, L5 (5 mg/kg), or TS58 (1 mg/kg) + L5 (5 mg/kg) in WT mice. Data represent the time from tail amputation to the time of blood flow cessation for longer than 10 seconds. Data are presented as the mean ± SD (n = 12). ***P < .001 vs PBS-treated WT mice; ###P < .001 vs L5-treated WT mice.

Levels of L5 and LOX-1, L5’s receptor, regulate infarct volume after ischemic stroke in mice. (A) Representative TTC stains of a coronal section of brain tissue for 1 mouse per group at 24 hours after focal cerebral ischemia (top) and the quantification of corresponding brain infarct volumes (bottom) in WT mice treated with PBS, L5 (5 mg/kg), or L1 (5 mg/kg) for 60 minutes before MCAO in addition to TS58 (1 mg/kg, a LOX-1 neutralizing antibody) 110 minutes after MCAO, or in LOX-1−/− mice treated with L5 or PBS. Data are presented as the mean ± SD (n = 8). **P < .01 vs PBS control; ###P < .001 vs L5-treated WT mice. (B) TS58 treatment improved performance in the tape removal test after ischemic stroke. The time needed to remove tape from both the contralateral and ipsilateral paws was recorded for sham-operated mice, WT mice that were treated either with PBS or L5 for 60 minutes before undergoing MCAO and reperfusion, and WT mice treated with L5 (5 mg/kg) for 60 minutes before MCAO and then treated with TS58 (1 mg/kg) 10 minutes before reperfusion. Data are presented as the mean ± SD (n = 8). ***P < .001 vs sham control; ###P < .001 vs L5-treated WT mice. (C) LOX-1 neutralizing antibody inhibits the L5-induced shortening of occlusion times for inducing thrombus formation in mesenteric venules of mice. Mice (WT and LOX-1−/−) were administered isovolumetric PBS solution, L5 (5 mg/kg), or TS58 (1 mg/kg) + L5 (5 mg/kg), and then mesenteric venules were selected for irradiation to induce microthrombus formation. (a) WT mice treated with PBS; (b) WT mice treated with L5; (c) WT mice treated with TS58 and L5; (d) LOX-1−/− mice treated with L5; (e) LOX-1−/− mice treated with PBS. Microscopic images (×400) obtained during the 143-second time period after the injection of fluorescent sodium (15 μg/kg) and transillumination in mice treated with PBS, L5 (5 mg/kg), or TS58 (1 mg/kg) + L5 (5 mg/kg). Arrows indicate platelet plug formation. Photographs are representative of 8 similar experiments. Bar, 30 μm. Data in the bar graph are presented as the mean ± SD (n = 8). ***P < .001 vs PBS control; ##P < .01 vs L5-treated WT mice. (D) TS58 treatment prolongs tail-bleeding time in L5-treated mice. Tail-bleeding time was determined after treatment with PBS or L5 (5 mg/kg) in LOX-1−/− mice and after treatment with PBS, L5 (5 mg/kg), or TS58 (1 mg/kg) + L5 (5 mg/kg) in WT mice. Data represent the time from tail amputation to the time of blood flow cessation for longer than 10 seconds. Data are presented as the mean ± SD (n = 12). ***P < .001 vs PBS-treated WT mice; ###P < .001 vs L5-treated WT mice.

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