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Profiling locomotor recovery: comprehensive quantification of impairments after CNS damage in rodents

Nature Methods volume 7, pages 701–708 (2010)Cite this article

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Abstract

Rodents are frequently used to model damage and diseases of the central nervous system (CNS) that lead to functional deficits. Impaired locomotor function is currently evaluated by using scoring systems or biomechanical measures. These methods often suffer from limitations such as subjectivity, nonlinearity and low sensitivity, or focus on a few very restricted aspects of movement. Thus, full quantitative profiles of motor deficits after CNS damage are lacking. Here we report the detailed characterization of locomotor impairments after applying common forms of CNS damage in rodents. We obtained many objective and quantitative readouts from rats with either spinal cord injuries or strokes and from transgenic mice (Epha4−/−) during skilled walking, overground walking, wading and swimming, resulting in model-specific locomotor profiles. Our testing and analysis method enables comprehensive assessment of locomotor function in rodents and has broad application in various fields of life science research.

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Figure 1: Experimental setup for detailed evaluation of locomotor function in rodents after different forms of CNS damage.
Figure 2: Skilled locomotion after CNS damage.
Figure 3: Overground walking after CNS damage.
Figure 4: Wading after CNS damage.
Figure 5: Swimming after CNS damage.

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Acknowledgements

We dedicate this work to the memory of our late colleague and friend Eva Hochreutener, who contributed excellent graphical work and suggestions essential to this study. We thank R. Schöb and P. Scheuble for IT support and S. Giger for construction of the behavioral testing system, L. Schnell for her pioneering work on behavior testing and evaluation in our laboratory, M. Petrinovic for help with mouse testing, R. Klein (Department of Molecular Neurobiology, Max Planck Institute of Neurobiology, Martinsried) for providing the Epha4−/− mice and members of the software company ALEA Solutions GmbH for close collaboration and for the development of the tracking software. This study was supported by grants of the Swiss National Science Foundation (31-63633.00 and 3100AO-122527/1), the National Centre for Competence in Research 'Neural Plasticity and Repair' of the Swiss National Science Foundation, the Spinal Cord Consortium of the Christopher and Dana Reeve Foundation and the Framework Program 7 EU Collaborative Project Spinal Cord Repair.

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Author notes

  1. Björn Zörner and Linard Filli: These authors contributed equally to this work.

Authors and Affiliations

  1. Brain Research Institute, University and ETH Zurich, Zurich, Switzerland

    Björn Zörner, Linard Filli, Michelle L Starkey, Roman Gonzenbach, Hansjörg Kasper, Martina Röthlisberger & Martin E Schwab

  2. Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland

    Marc Bolliger

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Contributions

B.Z. and L.F. designed the study, developed the testing setup, performed surgeries, collected and analyzed data, made the figures and prepared the manuscript. M.L.S. developed stroke lesions, performed surgeries and prepared the manuscript. R.G. developed the EMG setup, performed the recordings and collected and analyzed data. H.K. developed the testing setup and developed software. M.R. performed surgeries and collected and analyzed data. M.B. developed software and collected and analyzed data. M.E.S. designed the study, prepared the manuscript, and conceived and supervised the study.

Corresponding author

Correspondence to Björn Zörner.

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Competing interests

B.Z., L.F., M.L.S., H.K. and M.E.S. consult with the company TSE Systems GmbH for the development of a commercially available version of the rodent testing setup.

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Zörner, B., Filli, L., Starkey, M. et al. Profiling locomotor recovery: comprehensive quantification of impairments after CNS damage in rodents. Nat Methods 7, 701–708 (2010). https://doi.org/10.1038/nmeth.1484

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