Dissemination of refinements in mouse experimental stroke models to the scientific community

Cerebral stroke is the third cause of death and the most common cause of adult disability. However, current treatments are limited both in terms of utility and effectiveness. Efficacy of stroke interventions are tested using rodent middle cerebral artery occlusion (MCAO) models of focal brain ischemia but these have a poor record of translating into clinically effective treatments. The majority of experimental stroke studies use lesion volume as the primary outcome measure. However, variability in MCAO lesion volume is high with significant differences generally tested using parametric analyses which require a normal data distribution. Data from my laboratory over the last 10 years (and confirmed by others) shows that MCAO lesion volume data is not normally distributed and results in a bimodal distribution of small (purely striatal) and large (striato-cortical) lesions. Thus, previous studies using parametric tests, implicitly or explicitly based on an assumption of normal distribution, are likely to have been underpowered and analysed inappropriately thus decreasing their chance of detecting effective drug treatments.

In our previous NC3Rs grant (REF NC/M000117/1 to CG) we have demonstrated that an alternative surgical approach to induce experimental stroke by middle cerebral artery occlusion (MCAO) in mice led to improved welfare and reduced variability in lesion volume. Importantly, such reduced variability should help ensure that lesion volume sizes, within groups, are more consistent and appropriate a priori power calculations are performed. For example, using the data obtained in that study our power analysis shows that fewer animals per group are required to demonstrate a 30% reduction in lesion volume following our new approach compared to the traditional approach.

• Research Review: Blood flow in mouse stroke models
• Further Funding: NC3Rs PhD Studentship, Improving the welfare and monitoring of rodents undergoing experimental stroke studies, October 2015, £90,000
• Further Funding: NC3Rs Pilot Study Grant, Determining the source of variability within experimental stroke models,  November 2014, £74,586