Neuroprotective Effect of Darbepoetin Alfa, a Novel Recombinant Erythropoietic Protein, in Focal Cerebral Ischemia in Rats by Ludmila Belayev, Larissa.

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Neuroprotective Effect of Darbepoetin Alfa, a Novel Recombinant Erythropoietic Protein, in Focal Cerebral Ischemia in Rats by Ludmila Belayev, Larissa Khoutorova, Weizhao Zhao, Alexey Vigdorchik, Andrey Belayev, Raul Busto, Ella Magal, and Myron D. Ginsberg Stroke Volume 36(5):1065-1070 May 1, 2005 Copyright © American Heart Association, Inc. All rights reserved.

Figure 1. Total neurological score (normal score=0; maximal score=12) during MCA occlusion and at various times after treatment. Figure 1. Total neurological score (normal score=0; maximal score=12) during MCA occlusion and at various times after treatment. At the earlier time points (up to 72 hours), data from the 3-day and 14-day survival groups were pooled for analysis (vehicle, n=13; darbepoetin alfa-treated, n=16). For time points >72 hours: vehicle, n=6 and darbepoetin alfa-treated, n=8. Values are means±SEM. *P<0.05 vs corresponding vehicle-group by repeated-measures ANOVA followed by Bonferroni tests. DP-Alfa indicates darbepoetin alfa. Ludmila Belayev et al. Stroke. 2005;36:1065-1070 Copyright © American Heart Association, Inc. All rights reserved.

Figure 2. Rostrocaudal distribution of cortical (A) and subcortical (B) areas of infarction at 9 coronal levels in the 3-day and 14–day survival groups. Figure 2. Rostrocaudal distribution of cortical (A) and subcortical (B) areas of infarction at 9 coronal levels in the 3-day and 14–day survival groups. Data are presented as means±SEM (3-day series: vehicle, n=7 and darbepoetin alfa-treated, n=8; 14-day series: vehicle, n=6 and darbepoetin alfa-treated, n=8). *P<0.05 vs corresponding vehicle groups, repeated-measures ANOVA followed by Bonferroni tests. DP-Alfa indicates darbepoetin alfa. Ludmila Belayev et al. Stroke. 2005;36:1065-1070 Copyright © American Heart Association, Inc. All rights reserved.

Figure 3. Total corrected infarct volume in vehicle- and darbepoetin alfa-treated 3-day (vehicle, n=7 and darbepoetin alfa-treated, n=8) and 14-day (vehicle, n=6 and darbepoetin alfa-treated, n=8) survival groups. Figure 3. Total corrected infarct volume in vehicle- and darbepoetin alfa-treated 3-day (vehicle, n=7 and darbepoetin alfa-treated, n=8) and 14-day (vehicle, n=6 and darbepoetin alfa-treated, n=8) survival groups. Data are presented as means±SEM. *P<0.05 vs corresponding vehicle group. DP-Alfa indicates darbepoetin alfa. Ludmila Belayev et al. Stroke. 2005;36:1065-1070 Copyright © American Heart Association, Inc. All rights reserved.

Figure 4. Infarct frequency maps at 9 coronal levels (bregma +5 Figure 4. Infarct frequency maps at 9 coronal levels (bregma +5.2 mm to −7.3 mm) in the 3-day (A, B, C) and in the 14-day survival groups (D, E, F). Figure 4. Infarct frequency maps at 9 coronal levels (bregma +5.2 mm to −7.3 mm) in the 3-day (A, B, C) and in the 14-day survival groups (D, E, F). The color bars in (A), (B), (D), and (E) depict percentages of animals having infarction at each pixel location. C and F, Results of Fisher exact tests performed on a pixel-by-pixel basis to compare the vehicle-treated and darbepoetin alfa-treated groups; color scales denote (1−p), where p is the significance level of intergroup difference. The lower threshold of the color bars has been set to 0.95 (1−p), so that colored pixels are those with P<0.05. The infarct is large in vehicle-treated animals but markedly reduced in darbepoetin alfa-treated animals in the 14-day series. Ludmila Belayev et al. Stroke. 2005;36:1065-1070 Copyright © American Heart Association, Inc. All rights reserved.