Demonstration of therapeutic window of Cerebrolysin in embolic stroke: A prospective, randomized, blinded, and placebo-controlled study. Issue 6 (August 2017)

• Record Type: Journal Article
• Authors: Zhang, Li; Chopp, Michael; Lu, Mei; Zhang, Talan; Li, Chao; Winter, Stefan; Brandstaetter, Hemma; Doppler, Edith; Meier, Dieter; Pabla, Pardeep; Zhang, Zheng G
• Is Part Of: International journal of stroke. Volume 12:Issue 6(2017)
• Page Start: 628
• Page End: 635
• Publication Date: 2017-08
• Subjects: Cerebrolysin -- ischemic stroke -- treatment -- middle cerebral artery occlusion -- neurological outcome -- recovery -- brain infarction -- therapeutic window -- embolic stroke; 616.8005
• DOI: 10.1177/1747493017702665
• Languages: English
• ISSNs: 1747-4930

Abstract

Background and aims: In an effort to characterize the effects of Cerebrolysin for treatment of stroke that are essential for successful clinical translation, we have demonstrated that Cerebrolysin dose dependently enhanced neurological functional recovery in experimental stroke. Here, we conduct a prospective, randomized, placebo-controlled, blinded study to examine the therapeutic window of Cerebrolysin treatment of rats subjected to embolic stroke. Methods: Male Wistar rats age 3–4 months (n = 100) were subjected to embolic middle cerebral artery occlusion. Animals were randomized to receive saline or Cerebrolysin daily for 10 consecutive days starting 4, 24, 48, and 72 h after middle cerebral artery occlusion. Neurological outcome was measured weekly with a battery of behavioral tests (adhesive removal test, modified neurological severity score (mNSS), and foot-fault test). Global test was employed to assess Cerebrolysin effect on neurological recovery with estimation of mean difference between Cerebrolysin and control-treated groups and its 95% confidence interval in the intent-to-treat population, where a negative value of the mean difference and 95% confidence interval < 0 indicated a significant treatment effect. All rats were sacrificed 28 days after middle cerebral artery occlusion and infarct volume was measured. Results: Cerebrolysin treatment initiated within 48 h after middle cerebral artery occlusion onset significantly improved functional outcome; mean differences and 95% confidence interval were −11.6 (−17.7, −5.4) at 4 h, −7.1 (−13.5, −0.8) at 24 h, −8.4 (−14.2, −8.6) at 48 h, and −4.9 (−11.4, 1.5) at 72 h. There were no differences on infarct volume and mortality rate among groups. Conclusions: With a clinically relevant rigorous experimental design, our data demonstrate that Cerebrolysin treatment effectively improves stroke recovery when administered up to 48 h after middle cerebral artery occlusion.