Abstract WP102: Cerebrolysin Improves Neurological Outcome in Rats After Acute Stroke: a Prospective, Randomized, Blinded, Placebo-controlled Study
Background and Purpose: Cerebrolysin is a mixture of neuropeptides and free amino acids that exert potent neuroprotective and neurorestorative properties in experimental models of stroke. We conducted a prospective, randomized, double-blind and placebo controlled dose-response study of Cerebrolysin in both male and female rats after embolic stroke.
Methods: Randomization schemas were generated using nQuery3.0. Male and female Wistar rats (3-4 months) were subjected to embolic middle cerebral artery occlusion (MCAO). After confirming successful stroke with a 5 point neurological scale (Longa scale) at 3h after MCAO, ischemic rats were treated with Cerebrolysin at doses of (0.8, 2.5, 5.0, 7.5ml/kg) and saline based on the randomization schema 4h after MCAO and continued daily for a total of 10 consecutive days. The primary outcome was neurologic outcome measured by adhesive removal test, foot-fault test, and modified neurological severity score at day 28, lesion volume and mortality were secondary and safety outcomes, respectively.
Results: There was a significant dose effect of Cerebrolysin on neurological functional improvement 28 day after MCAO. Cerebrolysin at a dose of ≥ 2.5ml/kg significantly (P<0.001) improved neurological outcome (Mean Estimate with 95%CL): 0.8ml/kg: 6.2 (-6.0/18.4), 2.5ml/kg: -28.9 (-41.6/-16.2), 5.0ml/kg: -33.4 (-45.0/-21.7), 7.5ml/kg: -36.3 (-48.2/-24.4). Higher doses (≥2.5ml/kg) resulted in better recovery; however, differences between effective doses were not significant. Treatment with 5ml/kg reduced lesion volume (19.5±8.9%) compared with saline treated rats (27.7±11.9%, P=0.016). No treatment gender interactions were found and there were no differences on mortality rate.
Conclusion: Cerebrolysin in a dose-dependent manner significantly improved neurological outcomes in ischemic rats. Cerebrolysin at a dose of 5ml/kg reduced infarct volume. Our data on Cerebrolysin efficacy demonstrate the feasibility of a preclinical study setup following a randomized, placebo controlled, and blinded design with a clinical relevant treatment scheme.
Author Disclosures: L. Zhang: None. M. Chopp: None. M. Lu: None. T. Zhang: None. P. Pabla: None. S. Winter: None. E. Doppler: None. D. Meier: None. Z. Zhang: None.
- © 2016 by American Heart Association, Inc.