Tos Pierluigi, Ronchi Giulia, Papalia Igor, Sallen Vera, Legagneux Josette, Geuna Stefano, Giacobini-Robecchi Maria G
Reconstructive Microsurgery Unit, Department of Orthopedics, C.T.O. Hospital, Turin 10126, Italy.
Int Rev Neurobiol. 2009;87:47-79. doi: 10.1016/S0074-7742(09)87004-9.
This paper addresses several basic issues that are important for the experimental model design to investigate peripheral nerve regeneration. First, the importance of carrying out adequate preliminary in vitro investigation is emphasized in light of the ethical issues and with particular emphasis on the concept of the Three Rs (Replacement, Reduction, and Refinement) for limiting in vivo animal studies. Second, the various options for the selection of the animal species for nerve regeneration research are reviewed. Third, the two main experimental paradigms of nerve lesion (axonotmesis vs. neurotmesis followed by microsurgical reconstruction) are critically outlined and compared. Fourth, the various nerve models that have most commonly been employed are overviewed focusing in particular on forearm mixed nerves and on behavioural tests for assessing their function: the ulnar test and the grasping test which is useful for assessing both median and radial nerves in the rat. Finally, the importance of considering the influence of various factors and diseases which could interfere with the nerve regeneration process is emphasized in the perspective of a wider adoption of experimental models which more closely mimic the environmental and clinical conditions found in patients.
本文探讨了几个对于研究周围神经再生的实验模型设计至关重要的基本问题。首先，鉴于伦理问题，强调了进行充分的初步体外研究的重要性，并特别强调了用于限制体内动物研究的“3R”原则（替代、减少和优化）。其次，回顾了神经再生研究中选择动物物种的各种选项。第三，批判性地概述并比较了神经损伤的两种主要实验范式（轴突断裂与神经断裂后显微外科重建）。第四，概述了最常用的各种神经模型，特别关注前臂混合神经以及评估其功能的行为测试：尺神经测试和用于评估大鼠正中神经和桡神经的抓握测试。最后，从更广泛采用更紧密模拟患者所处环境和临床状况的实验模型的角度出发，强调了考虑可能干扰神经再生过程的各种因素和疾病的影响 的重要性。
