International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, British Columbia, Canada.
Exp Neurol. 2010 Feb;221(2):285-95. doi: 10.1016/j.expneurol.2009.11.006. Epub 2009 Nov 18.
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.
尽管在急性脊髓损伤患者的临床治疗方面已经取得了很大进展,但目前仍没有可靠有效的治疗方法来最小化继发性损伤并改善神经功能预后。由于开发新的急性 SCI 药物或生物疗法需要时间和费用,因此鼓励开发基于已在临床使用的药物的神经保护疗法,这些药物具有良好的人类安全性和药代动力学特征。他汀类药物是最常用的降脂药物类别,最近人们已经认识到他汀类药物还具有强大的免疫调节和抗炎作用。本文描述了一系列旨在评估辛伐他汀和阿托伐他汀的比较神经保护作用的实验。我们在第一个实验中观察到辛伐他汀具有有希望的神经获益信号,但在随后的三个实验中重复尝试复制该效果时,我们未能发现任何行为或组织学改善。我们的结论是,当在干预后 1 小时延迟给予时,以前其他研究人员在不同神经疾病中报告有效的口服或皮下给予辛伐他汀或阿托伐他汀的剂量,不会在胸段挫伤损伤模型(OSU 撞击器)中带来显著的神经获益。我们认为,在考虑将其转化为人类 SCI 之前,有必要进一步进行阿托伐他汀和辛伐他汀的临床前研究。