Improving the welfare and monitoring of rodents undergoing experimental stroke studies

Middle cerebral artery occlusion (MCAO) is the most common method of inducing ischaemic stroke in laboratory rodents and has a significant impact on their welfare. This thesis investigated three refinements in experimental stroke studies. Firstly, the role of environmental enrichment was investigated using preference tests, measure of neurogenesis and functional outcomes. Mice demonstrated consistent avoidance of the enriched environment yet enrichment did increase hippocampal cell proliferation. Rats showed no significant preference for the standard environment at any time point but experienced no increase in neurogenesis in response to enriched housing. Differences between sexes and light cycle phases were observed in both mice and rats. Thus, these findings demonstrate the complexity of environmental enrichment and highlight the need to tailor protocols to the animals being used. When delivered prior to and/or following MCAO, enrichment did not significantly improve outcome in welfare measures or behavioural tests, although changing environment post-MCAO did appear to be detrimental, and increased neurogenesis accompanied post-stroke enrichment. Secondly, the benefit of a pre-stroke surgical intervention was investigated. The craniotomy surgery, has been shown to improve survival and weight loss in hypertensive rats. No effect of the intervention was seen on lesion volume or brain swelling and no welfare benefit was seen in normotensive rats. Finally, the ability to monitor welfare using temperature and activity measurements from telemetry devices was investigated. Body temperature of young rats was significantly altered by MCAO surgery and species differences were found, with mice having significantly lower body temperature than young rats. Correlations between physiological parameters and outcome measures post-MCAO were promising, particularly neurological score, which showed significant correlations with body temperature of mice and rats. Overall, this thesis presents promising results, but further work is required to draw concrete conclusions on refining experimental stroke studies to improve animal welfare.