Distal Occlusion of the Middle Cerebral Artery in Mice: Are We Ready to Assess Long-Term Functional Outcome?

Rodent animal models of stroke are widely used with brain ischemia inducible by various occlusion methods. Permanent or transient occlusion of the distal portion of the middle cerebral artery (MCAO) offers a reproducible model with low mortality rates, and it is the most likely model of choice for mid- and long-term studies to assess neurorepair or long-term effects of neuroprotective drugs. Therefore, a measurable and stable neurological assessment would be required to evaluate sensorimotor and cognitive deficits at short and long terms as suggested by the Stroke Therapy Academic Industry Roundtable preclinical recommendations. We review the usefulness of different tests used to measure functional outcome after distal MCAO in mice and further sustain these data with our own multilaboratories' experience. Results show that several tests were suitable to detect neurological deterioration at short term. Grip strength and latency to move have shown some usefulness at long term, with important differences between strains, while less clear are the data for the corner test. Important strain differences in terms of infarct volume are also reported in this study. Statistical power analysis and sample size calculation of our data confirmed the value of grip strength and latency to move tests but suggest that larger sample size would be required. In conclusion, there are no robust data supporting the use of a specific behavior test to assess long-term functional outcome after distal MCAO in mice. This is an important limitation since translational basic research should provide data to help further clinical trial evaluation. New multicenter studies with larger sample size and specific mouse strains are needed to confirm the validity of tests, such as the corner, latency to move or grip strength.