METHODS: In the gerbil BCAO model,
isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after
ischemia (n = 10). Corresponding controls received vehicle (n = 10), and
sham-operated animals received no treatment (n = 6). Locomotor activity and histological assessments were made at 4 days after
ischemia. In the rat photothrombotic occlusion model,
isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after
ischemia (n = 10), and corresponding controls (n = 10) received vehicle. Histological assessment was made at 7 days after
ischemia. In the mouse MCAO model,
isradipine was also administered at 2.5 mg/kg i.p. as a single dose 60 minutes after
ischemia. Histological assessments were made at 1 (n = 13), 2 (n = 9), and 4 (n = 9) days after
ischemia. Vehicle numbers were n = 10, n = 6, and n = 8, respectively.
Isradipine and SB201823A were also examined using a combined preischemia and postischemia regimen.
Isradipine was administered at 2.5 mg/kg i.p. before occlusion, 1.25 mg/kg i.p. 1 hour after occlusion, 1.25 mg/kg i.p. 2 hours after occlusion, and 2.5 mg/kg twice a day for 3 days after occlusion (n = 16). Corresponding controls received vehicle at the same time points (n = 14). SB201823A was administered 30 minutes before occlusion, 30 minutes after occlusion, and twice daily for 3 days (n = 12). Corresponding controls received vehicle (n = 9). Histological assessment was performed at 4 days after
ischemia.
RESULTS: When given after
ischemia,
isradipine failed to affect lesion volume in both the rat and mouse models. In the gerbil, locomotor hyperactivity and hippocampal cell loss were unaffected. Given before and after
ischemia in the mouse,
isradipine was also ineffective, whereas SB201823A produced a significant reduction in lesion volume.
CONCLUSIONS: