Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), National Study Center for Trauma and Emergency Medical Systems, University of Maryland School of Medicine, Baltimore, MD, USA.
Trends Pharmacol Sci. 2010 Dec;31(12):596-604. doi: 10.1016/j.tips.2010.09.005. Epub 2010 Oct 29.
Traumatic brain injury (TBI) causes secondary biochemical changes that contribute to subsequent tissue damage and associated neuronal cell death. Neuroprotective treatments that limit secondary tissue loss and/or improve behavioral outcome have been well established in multiple animal models of TBI. However, translation of such neuroprotective strategies to human injury have been disappointing, with the failure of more than thirty controlled clinical trials. Both conceptual issues and methodological differences between preclinical and clinical injury have undoubtedly contributed to these translational difficulties. More recently, changes in experimental approach, as well as altered clinical trial methodologies, have raised cautious optimism regarding the outcomes of future clinical trials. Here we critically review developing experimental neuroprotective strategies that show promise, and we propose criteria for improving the probability of successful clinical translation.
创伤性脑损伤（TBI）会引起继发性生化变化，导致随后的组织损伤和相关神经元细胞死亡。在多种 TBI 动物模型中，已经证实了许多神经保护治疗方法可以限制继发性组织损失和/或改善行为结果。然而，这些神经保护策略向人类损伤的转化令人失望，三十多项对照临床试验都失败了。临床损伤与临床前损伤之间的概念问题和方法学差异无疑促成了这些转化困难。最近，实验方法的改变以及临床试验方法的改变，使人们对未来临床试验的结果持谨慎乐观的态度。在这里，我们批判性地回顾了有前景的正在发展的实验性神经保护策略，并提出了提高成功临床转化概率的标准。
