Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury

被引:22
作者
Mann, Cody M. [1 ]
Lee, Jae H. T. [1 ]
Hillyer, Jessica [1 ]
Stammers, Anthea M. T. [1 ]
Tetzlaff, Wolfram [1 ,3 ]
Kwon, Brian K. [1 ,2 ]
机构
[1] Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Dept Orthopaed, CNOSP, Vancouver, BC V5Z 1M9, Canada
[3] Univ British Columbia, Dept Zool, Vancouver, BC V5Z 1M9, Canada
关键词
Simvastatin; Atorvastatin; Neuroprotection; Spinal cord injury; NITRIC-OXIDE SYNTHASE; TRAUMATIC BRAIN-INJURY; MORPHOLOGICAL CONSEQUENCES; NEUROPROTECTIVE AGENT; INFLAMMATORY RESPONSE; LOCOMOTOR RECOVERY; ISCHEMIC BRAIN; STATINS; RATS; ERYTHROPOIETIN;
D O I
10.1016/j.expneurol.2009.11.006
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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 oil 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 OF 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 I-h delay in intervention. We contend that further preclinical investigation of atorvastatin and simvastatin is warranted before considering their translation into human SCI. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:285 / 295
页数:11
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