Abstract WP105: An Effective Delayed Treatment for Ischemic Stroke Uses Fluoxetine and Simvastatin
For more than 90% of ischemic stroke patients there exists no standardized drug treatment other than giving aspirin or beginning statin treatment for the prevention of future strokes. The purpose of this study was to develop a delayed pharmacological treatment for ischemic stroke, utilizing a combination of drugs that would enhance adult neurogenesis and brain-derived neurotrophic factor. An endothelin-induced stroke was produced in 10-12 month old rats, which have previously been trained on Montoya Staircase and Forelimb Asymmetry tests. Combination drug treatments were tested against vehicle controls, beginning 20-26 hours after stroke induction and continuing for 31 days. Functional tests were performed at various times post-stroke. Daily treatments of 5 mg/kg fluoxetine in combination with 0.5 mg/kg simvastatin and 20 mg/kg ascorbic acid produced a 19-fold increase in neurogenesis (P=0.001 compared to vehicle control), while fluoxetine alone produced a 10-fold increase in neurogenesis (P=0.007 compared to vehicle control). This combination drug treatment results in almost complete functional recovery as measured by Montoya Staircase (mean recovery to 85% of pre-stroke function, P=0.023) and Forelimb Asymmetry tests (mean recovery to 90% of pre-stroke function, P=0.041 and P= 0.05) in 10-12 month old stroked female Long Evans rats. Additional testing of 5 mg/kg fluoxetine and 20 mg/kg ascorbic acid drug combination as a delayed post-stroke treatment has only given half of the functional recovery seen when all three drugs are included, indicating that the statin is essential for full recovery. Fluoxetine is likely to be the other essential component of this combination treatment as it alone resulted in a significant increase in adult neurogenesis.
- © 2012 by American Heart Association, Inc.