An Effective Delayed Treatment for Ischemic Stroke uses Drug Combination of Fluoxetine, Simvastatin and Ascorbic Acid

Abstract

<p>Only 8.3% of ischemic stroke patients make it to the hospital in the narrow window of time to receive the clot-buster drug, tPA. For more than 90% of ischemic stroke patients there exists no standardized hospital treatment other than giving aspirin. The purpose of this study was to develop a delayed pharmacological treatment for ischemic stroke, capable of use by 90% of ischemic stroke patients, utilizing a combination of drugs that would enhance 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 is-fold increase in neurogenesis (P=O.OOl 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 prestroke function, P=0.041 and P= 0.05) in 10-12 month old stroked female 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 simvastatin is essential for full recovery. This unique drug combination of fluoxetine, simvastatin, and ascorbic acid results in almost complete functional recovery when given up to 26 hours after ischemic stroke induction.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 8, 2011</p>