BSF468248 is a novel potent
complement C1 inhibitor. To determine whether
BSF468248 is effective against focal
cerebral ischemia, we evaluated the change of cerebral blood flow (CBF) and
infarction volume using a photochemically-induced cortical vein occlusion model in rats in blind studies. In 22 Wistar rats, two adjacent cortical veins were occluded by photochemical
thrombosis and fiberoptic illumination under controlled
anesthesia and ventilation. Just after the occlusion,
BSF468248 or physiological saline was administrated. In the low-dose study, a treatment group (n = 7) was administered
BSF468248 1 mg/kg bolus and 1 mg/kg continuously for 30 min. The same volume of saline was given to a vehicle group (n = 5). In the high-dose study, a treatment group (n = 5) was administrated
BSF468248 1 mg/kg bolus and 12 mg/kg continuously for 180 min. The same volume of saline was given to a vehicle group (n = 5). During the experiment, regional cerebral blood flow (rCBF) was measured in both the low-dose study (120 min) and the high-dose study (180 min). Seven days after the experiment, the animals were killed in order to evaluate the
infarct volume. The rCBF at the end of the experiment showed a similar decrease in both the low-dose study (at 120 min: treatment group: 66.5 +/- 10.2%; vehicle group: 69.3 +/- 10.2%) and the high-dose study (at 180 min: treatment group: 62.1 +/- 7.5%; vehicle group: 65.1 +/- 12.3%), with no significant differences (t-test). The
infarct volume also showed no significant difference in either group of the low-dose study (treatment group: 3.46 +/- 0.84 mm3; vehicle group: 3.56 +/- 1.40 mm3) or the high-dose study (treatment group: 2.27 +/- 0.43 mm3; vehicle group: 1.76 +/- 0.31 mm3). Our study found that
BSF468248 is not effective in improving the rCBF and the
infarct volume following focal
cerebral ischemia.