title: Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury.
abstract: Although much progress has been made in the clinical care of patients with acute spinal cord injuries, there are no reliably effective treatments, which minimize secondary damage and improve neurologic outcome. The time and expense needed to establish de novo pharmacologic or biologic therapies for acute SCI has encouraged the development of neuroprotective treatments based on drugs that are already in clinical use and, therefore, have the advantage of a well-characterized safety and pharmacokinetic profile in humans. Statins are the most commonly prescribed class of lipid-lowering drugs, and recently, it has been recognized that statins also have powerful immunomodulatory and anti-inflammatory effects. This paper describes a series of experiments that were performed to evaluate the comparative neuroprotective effects of simvastatin and atorvastatin. We observed a promising signal of neurologic benefit with simvastatin in our first experiment, but in repeated attempts to replicate that effect in three subsequent experiments, we failed to reveal any behavioral or histologic improvements. We would conclude that simvastatin given orally or subcutaneously at doses previously reported by other investigators to be effective in different neurologic conditions does not confer a significant neurologic benefit in a thoracic contusion injury model (OSU Impactor) when administered with a 1-h delay in intervention. We contend that further preclinical investigation of atorvastatin and simvastatin is warranted before considering their translation into human SCI.
authors.affiliation: International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cody M
authors.initials: CM
authors.lastname: Mann
authors.forename: Jae H T
authors.initials: JH
authors.lastname: Lee
authors.forename: Jessica
authors.initials: J
authors.lastname: Hillyer
authors.forename: Anthea M T
authors.initials: AM
authors.lastname: Stammers
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tetzlaff
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kwon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000069059:Atorvastatin; D001557:Benzenesulfonates; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D053331:Ectodysplasins / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005526:Food, Formulated; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012445:Sacrococcygeal Region; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications*
chemical_list: D001557:Benzenesulfonates; D019422:Dietary Sucrose; D053331:Ectodysplasins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C082131:Ensure formulated food; C010332:solochrome cyanine R; D000069059:Atorvastatin; D019821:Simvastatin