Braeuninger Stefan, Kleinschnitz Christoph
Department of Neurology, Julius-Maximilians-Universitaet Wuerzburg, Josef-Schneider-Str. 11, 97080 Wuerzburg, Germany.
Exp Transl Stroke Med. 2009 Nov 25;1:8. doi: 10.1186/2040-7378-1-8.
Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure.
局灶性脑缺血的啮齿动物模型是实验性中风研究的重要工具。它们极大地增进了我们对中风损伤机制的理解,并有助于确定潜在的治疗靶点。然而,大量物质,尤其是数量众多的假定神经保护剂,在临床前中风研究中已显示出有效性,但在临床试验中却失败了。许多因素可能导致了这种从实验室到临床应用的失败。实验性中风研究质量的缺陷似乎常常与此有关。在本文中,我们回顾了最常见的局灶性脑缺血啮齿动物模型——大脑中动脉闭塞模型、光血栓形成模型和栓塞性中风模型——及其各自的优缺点,并探讨了临床前中风建模的质量问题以及转化失败的潜在原因。