The Timing of Fluoxetine, Simvastatin and Ascorbic Acid Administration in a Post-Ischemic Stroke Environment Affects Infarct Volume and Hemorrhagic Transformation Frequency

Previous animal experiments have indicated that administration of fluoxetine and simvastatin at 20-26 hours post-stroke decreases the volume of ischemic infarcts. This experiment expanded on previous experiments by adding ascorbic acid to the post-stroke regimen, initiating simvastatin pre-stroke, and adding a third initiation time frame (48-54 hours). Male retired breeder Sprague-Dawley rats were on simvastatin for 7 days prior to stroke induction. Combined medications of 5 milligrams/kilogram of fluoxetine, 1 milligram/kilogram of simvastatin and 20 milligrams/kilogram of ascorbic acid were orally administered at 6-12 hours, 20-26 hours, or 48-54 hours, respectively, following stroke induction. Adult rats that were treated 20-26 hours post-stroke showed a decrease in infarct volume (15.67 ± 5.622 millimeters cubed, P=0.0098) compared to the control. The combination of simvastatin, fluoxetine and ascorbic acid decreased the relative risk (RR=0.3704 (95% confidence interval 0.0987 to 1.3905, p-value = 0.1411) of bleeding after ischemic stroke if initiated 20-26 hours after stroke induction in rats