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

Translational Stroke Research - Tập 4 - Trang 297-307 - 2013
Anna Rosell1, Véronique Agin2, Mahbubur Rahman3, Anna Morancho1, Carine Ali2, Jari Koistinaho4, Xiaoying Wang5, Denis Vivien2, Markus Schwaninger3, Joan Montaner1
1Neurovascular Research Laboratory and Neurology Department, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
2Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP CYCERON, INSERM UMR-S U919, University Caen Basse-Normandie, Caen, France
3Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
4Department of Neurobiology, AI Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
5Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, USA

Tóm tắt

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.

Tài liệu tham khảo

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