A reassessment of a classic neuroprotective combination therapy for spinal cord injured rats: LPS/pregnenolone/indomethacin.
A reassessment of a classic neuroprotective combination therapy for spinal cord injured rats: LPS/pregnenolone/indomethacin.
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DOI：
10.1016/j.expneurol.2011.11.045
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发表时间：
2012-02
影响因子：
5.3
通讯作者：
Basso, D. Michele
中科院分区：
文献类型：
--
作者：
Popovich, Phillip G.;Tovar, C. Amy;Wei, Ping;Fisher, Lesley;Jakeman, Lyn B.;Basso, D. Michele
这些实验是作为NIH-NINDS合同的一部分完成的，该合同名为“研究能力-脊髓损伤（FORE-SCI）-复制设施”。我们的目标是复制Lloyd Guth博士及其同事发表的一篇论文中的数据，其中脂多糖、吲哚美辛和阿替诺龙的联合注射（本文称为LIP疗法）在脊髓损伤（SCI）的临床前模型中赋予显著的神经保护作用。具体地，发现损伤后注射组合LIP疗法显著减少损伤部位处/附近的组织损伤并显著改善运动功能的恢复。在本报告中，我们证实了Guth等人的主要观察结果，然而，LIP治疗的效果是适度的。具体而言，LIP治疗改善髓鞘和轴突保留，轴突发芽，同时减少病变空化。然而，使用历史（Tarlov评分）和更多当前评级量表（即，BBB评分），不受LIP治疗的影响。相反，更精确的功能恢复参数（网格行走期间的爪放置准确性）显示了显著的治疗效果。沿着描述了LIP治疗的神经保护作用的可能解释，以及为什么这项研究与Guth及其同事的研究之间的神经保护作用的程度可能不同的原因。
These experiments were completed as part of an NIH-NINDS contract entitled “Facilities of Research Excellence-Spinal Cord Injury (FORE-SCI)—Replication”. Our goal was to replicate data from a paper published by Dr. Lloyd Guth and colleagues in which combined injections of lipopolysaccharide, indomethacin and pregnenolone (referred to herein as LIP therapy) conferred marked neuroprotection in a pre-clinical model of spinal cord injury (SCI). Specifically, post-injury injection of the combination LIP therapy was found to significantly reduce tissue damage at/nearby the site of injury and significantly improve recovery of locomotor function. In this report, we confirm the primary observations made by Guth et al., however, the effects of LIP treatment were modest. Specifically, LIP treatment improved myelin and axon sparing, axonal sprouting while reducing lesion cavitation. However, spontaneous recovery of locomotion, as assessed using historical (Tarlov scoring) and more current rating scales (i.e., BBB scoring), was not affected by LIP treatment. Instead, more refined parameters of functional recovery (paw placement accuracy during grid walk) revealed a significant effect of treatment. Possible explanations for the neuroprotective effects of LIP therapy are described along with reasons why the magnitude of neuroprotection may have differed between this study and that of Guth and colleagues.
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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