The IMPROVE Guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Abstract

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information).

Keywords: 3Rs; animal welfare; guidelines; middle cerebral artery occlusion; stroke.

Figure 1.

(a) Mean body weight after 60 min of middle cerebral artery occlusion (MCAO) in the BL6 mouse strain (n = 10). Note the dramatic drop and slow recovery of body weight, whereas nonmanipulated control mice gain 1 to 2 g per week. (b) Correlation of infarct size with loss in body weight 72 h after 60 min of MCAO. Note the very tight correlation between infarct size and loss in body weight. 95% CIs for the population mean (regression). Reproduced with permission from Dirnagl.