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Translational Stroke Research

, Volume 4, Issue 3, pp 297–307 | Cite as

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

  • Anna RosellEmail author
  • Véronique Agin
  • Mahbubur Rahman
  • Anna Morancho
  • Carine Ali
  • Jari Koistinaho
  • Xiaoying Wang
  • Denis Vivien
  • Markus Schwaninger
  • Joan Montaner
Original Article

Abstract

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.

Keywords

Ischemia Mouse Distal MCAO Functional outcome 

Notes

Acknowledgments

A.R. is supported by the Miguel Servet program (CP09/00265) from the Spanish Ministry of Health (Instituto de Salud Carlos III). V.A., C.A. and D.V. works are supported by INSERM, French Ministry of Research and Technology, and Regional Council of Lower Normandy. The research leading to these results has received funding from the European Union’s Seventh Framework Program (FP7/2007-2013) under grant agreements No. 201024 and 202213 (European Stroke Network), the Spanish Ministry of Health (Instituto de Salud Carlos III, grant agreement No. PI10/00694, and RETICS program, RENEVAS network), and the ERANET-NEURON program from the Ministerio de Economía y Competitividad (grant agreement No. 2011-1352).

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Anna Rosell
    • 1
    Email author
  • Véronique Agin
    • 2
  • Mahbubur Rahman
    • 3
  • Anna Morancho
    • 1
  • Carine Ali
    • 2
  • Jari Koistinaho
    • 4
  • Xiaoying Wang
    • 5
  • Denis Vivien
    • 2
  • Markus Schwaninger
    • 3
  • Joan Montaner
    • 1
  1. 1.Neurovascular Research Laboratory and Neurology Department, Vall d’Hebron Research InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP CYCERONINSERM UMR-S U919, University Caen Basse-NormandieCaenFrance
  3. 3.Institute of Experimental and Clinical Pharmacology and ToxicologyUniversity of LübeckLübeckGermany
  4. 4.Department of Neurobiology, AI Virtanen Institute for Molecular SciencesUniversity of Eastern FinlandKuopioFinland
  5. 5.Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Neuroscience ProgramHarvard Medical SchoolBostonUSA

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