title: Increasing neurogenesis with fluoxetine, simvastatin and ascorbic Acid leads to functional recovery in ischemic stroke.
abstract: Less than 8.5% of ischemic stroke patients receive clot-busting drugs within the narrow time needed to reduce injury. Thus, there is need for an easily-accessible delayed post-stroke drug treatment to improve functional recovery. Various combinations of fluoxetine, simvastatin, and ascorbic acid were given to healthy rats to assess impact on neurogenesis versus controls. Fluoxetine combined with simvastatin and ascorbic acid produced a 19-fold increase in neurogenesis versus controls in healthy rats; fluoxetine alone produced 10-fold increase. We next tried a couple of drug combinations versus control in endothelin-induced stroked rats. Combined fluoxetine/ simvastatin/ascorbic acid treatment, given to stroked rats 20-26 hours after stroke induction and continued for 31 days, produced strong recovery as measured by Montoya staircase test (mean recovery to 85% of pre-stroke function) and Forelimb Asymmetry test (mean recovery to 90% of pre-stroke function). Fluoxetine and ascorbic acid without simvastatin only produced ~50% of recovery produced by the 3-drug combination. Our results indicate that combined treatment of Fluoxetine, simvastatin and ascorbic acid represents a promising delayed stroke treatment that greatly improves functional recovery in rats and warrants further study in human patient populations. This work formed the basis for a patent submission (US20130065924A1) Composition and method for treatment of neurodegeneration.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Corbett
authors.forename: Scott
authors.initials: S
authors.lastname: Sieber
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wyatt
authors.forename: Jenna
authors.initials: J
authors.lastname: Lizzi
authors.forename: Tiffany
authors.initials: T
authors.lastname: Flannery
authors.forename: Bethany
authors.initials: B
authors.lastname: Sibbit
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University, 3640 Colonel Glenn Highway, Dayton, Ohio 45435, United States. Adrian.corbett@wright.edu.
authors.forename: Saagar
authors.initials: S
authors.lastname: Sanghvi
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D019821:Simvastatin / Q000008:administration & dosage*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005473:Fluoxetine; D019821:Simvastatin; D001205:Ascorbic Acid