Institute for Translational Neurosurgery, Medical Faculty, RWTH Aachen University, 52074, Aachen, Germany.
Institute for Cardiovascular Sciences, University Hospital Bonn, 53127, Bonn, Germany.
Cell Mol Neurobiol. 2023 Nov;43(8):3965-3981. doi: 10.1007/s10571-023-01418-5. Epub 2023 Oct 20.
Subarachnoid hemorrhage is an acute life-threatening cerebrovascular disease with high socio-economic impact. The most frequent cause, the rupture of an intracerebral aneurysm, is accompanied by abrupt changes in intracerebral pressure, cerebral perfusion pressure and, consequently, cerebral blood flow. As aneurysms rupture spontaneously, monitoring of these parameters in patients is only possible with a time delay, upon hospitalization. To study alterations in cerebral perfusion immediately upon ictus, animal models are mandatory. This article addresses the points necessarily to be included in an animal project proposal according to EU directive 2010/63/EU for the protection of animals used for scientific purposes and herewith offers an insight into animal welfare aspects of using rodent models for the investigation of cerebral perfusion after subarachnoid hemorrhage. It compares surgeries, model characteristics, advantages, and drawbacks of the most-frequently used rodent models-the endovascular perforation model and the prechiasmatic and single or double cisterna magna injection model. The topics of discussing anesthesia, advice on peri- and postanesthetic handling of animals, assessing the severity of suffering the animals undergo during the procedure according to EU directive 2010/63/EU and weighing the use of these in vivo models for experimental research ethically are also presented. In conclusion, rodent models of subarachnoid hemorrhage display pathophysiological characteristics, including changes of cerebral perfusion similar to the clinical situation, rendering the models suited to study the sequelae of the bleeding. A current problem is low standardization of the models, wherefore reporting according to the ARRIVE guidelines is highly recommended. Animal welfare aspects of rodent models of subarachnoid hemorrhage. Rodent models for investigation of cerebral perfusion after subarachnoid hemorrhage are compared regarding surgeries and model characteristics, and 3R measures are suggested. Anesthesia is discussed, and advice given on peri- and postanesthetic handling. Severity of suffering according to 2010/63/EU is assessed and use of these in vivo models weighed ethically.
蛛网膜下腔出血是一种具有高社会经济影响的急性危及生命的脑血管疾病。最常见的原因是脑内动脉瘤破裂，伴随着颅内压、脑灌注压的突然变化，进而导致脑血流的变化。由于动脉瘤会自发性破裂，因此只能在患者住院后通过时间延迟来监测这些参数。为了研究出血后即刻脑灌注的变化，必须使用动物模型。本文根据欧盟指令 2010/63/EU 中关于保护用于科学目的的动物的规定，介绍了动物项目提案中必须包含的要点，并在此基础上介绍了使用啮齿动物模型研究蛛网膜下腔出血后脑灌注的动物福利方面。它比较了最常使用的两种啮齿动物模型——血管内穿孔模型和视交叉前及单一或双枕大池注射模型的手术、模型特征、优点和缺点。还讨论了麻醉、动物围手术期和术后处理的建议、根据欧盟指令 2010/63/EU 评估动物在手术过程中所承受的痛苦严重程度，以及权衡这些体内模型在实验研究中的伦理使用。总之，蛛网膜下腔出血的啮齿动物模型显示出与临床情况相似的病理生理学特征，包括脑灌注的变化，因此适合研究出血的后遗症。目前存在的一个问题是模型的标准化程度低，因此强烈建议按照 ARRIVE 指南进行报告。蛛网膜下腔出血啮齿动物模型的动物福利方面。比较了用于研究蛛网膜下腔出血后脑灌注的啮齿动物模型的手术和模型特征，并提出了 3R 措施。讨论了麻醉，并就围手术期和术后处理提供了建议。根据 2010/63/EU 评估了痛苦的严重程度，并从伦理角度权衡了这些体内模型的使用。
