Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury
| Autor: | Cody Mann, Jessica Hillyer, Wolfram Tetzlaff, A T Stammers, Jae H.T. Lee, Brian K. Kwon |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pain Threshold Simvastatin Atorvastatin Motor Activity Neuroprotection Rats Sprague-Dawley Central nervous system disease Developmental Neuroscience Spinal cord contusion Pharmacokinetics Dietary Sucrose medicine Animals Pyrroles Spinal cord injury Spinal Cord Injuries Pain Measurement Food Formulated Analysis of Variance Sacrococcygeal Region business.industry Drug Administration Routes Benzenesulfonates nutritional and metabolic diseases Ectodysplasins medicine.disease Spinal cord Rats Disease Models Animal medicine.anatomical_structure Neurology Heptanoic Acids Anesthesia Exploratory Behavior lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Nervous System Diseases business Psychomotor Performance medicine.drug |
| Zdroj: | Experimental Neurology. 221:285-295 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2009.11.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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