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      Validity and reliability of the CatWalk system as a static and dynamic gait analysis tool for the assessment of functional nerve recovery in small animal models

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          Abstract

          Introduction

          A range of behavioral testing paradigms have been developed for the research of central and peripheral nerve injuries with the help of small animal models. Following any nerve repair strategy, improved functional outcome may be the most important evidence of axon regeneration. A novel automated gait analysis system, the CatWalk , can measure dynamic as well as static gait patterns of small animals. Of most interest in detecting functional recovery are in particular dynamic gait parameters, coordination measures, and the intensity of the animals paw prints. This article is designed to lead to a more efficient choice of CatWalk parameters in future studies concerning the functional evaluation of nerve regeneration and simultaneously add to better interstudy comparability.

          Methods

          The aims of the present paper are threefold: (1) to describe the functional method of CatWalk gait analysis, (2) to characterize different parameters acquired by CatWalk gait analysis, and to find the most frequently used parameters as well as (3) to compare their reliability and validity throughout the different studies.

          Results

          In the reviewed articles, the most frequently used parameters were Swing Duration (30), Print Size (27), Stride Length (26), and Max Contact Area (24). Swing Duration was not only frequently used but was also the most reliable and valid parameter. Therefore, we hypothesize that Swing Duration constitutes an important parameter to be chosen for future studies, as it has the highest level of reliability and validity.

          Conclusion

          In conclusion, CatWalk can be used as a complementary approach to other behavioral testing paradigms to assess clinically relevant behavioral benefits, with the main advantage that this system demonstrates both static and dynamic gait parameters at the same time. Due to limited reliability and validity of certain parameters, we recommend that only the most frequently assessed parameters should be used in the future.

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          Most cited references73

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          An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks.

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            Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury.

            Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 degrees C, necessitating the use of repeated injections or local infusions for a period of days to weeks. These infusion systems are invasive, infection-prone, and clinically problematic. To overcome this limitation, we have thermostabilized chABC and developed a system for its sustained local delivery in vivo, obviating the need for chronically implanted catheters and pumps. Thermostabilized chABC remained active at 37 degrees C in vitro for up to 4 weeks. CSPG levels remained low in vivo up to 6 weeks post-SCI when thermostabilized chABC was delivered by a hydrogel-microtube scaffold system. Axonal growth and functional recovery following the sustained local release of thermostabilized chABC versus a single treatment of unstabilized chABC demonstrated significant differences in CSPG digestion. Animals treated with thermostabilized chABC in combination with sustained neurotrophin-3 delivery showed significant improvement in locomotor function and enhanced growth of cholera toxin B subunit-positive sensory axons and sprouting of serotonergic fibers. Therefore, improving chABC thermostability facilitates minimally invasive, sustained, local delivery of chABC that is potentially effective in overcoming CSPG-mediated regenerative failure. Combination therapy with thermostabilized chABC with neurotrophic factors enhances axonal regrowth, sprouting, and functional recovery after SCI.
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              The assessment of locomotor function in spinal cord injured rats: the importance of objective analysis of coordination.

              The Basso, Beattie and Bresnahan (BBB) locomotor rating scale is the most widely used open field test and has been accepted as a valid way to assess locomotor function after spinal cord contusion injury in the rat. A limitation within the BBB locomotor rating scale is the correct assessment of forelimb (FL)-hindlimb (HL) coordination. This limitation can have major implications for the final assessment of locomotor function. In the present study, we show an objective method to assess coordination based on the regularity index (RI), achieved through the use of the CatWalk method. The RI grades the degree of coordination as the result of the number of normal step sequence patterns multiplied by four and divided by the total amount of paw placements. Using the RI, single walkway crossings can be objectively analyzed on coordination. Integration of the CatWalk based coordination into the BBB scale indicates that objective analysis of coordination results in reliable and more sensitive assessment of locomotor function. This new method has been tested successfully in determination of positive effects of enriched housing on functional recovery after spinal cord injury (SCI).
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                Author and article information

                Contributors
                Elisabeth.Kappos@usb.ch
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                18 May 2017
                July 2017
                : 7
                : 7 ( doiID: 10.1002/brb3.2017.7.issue-7 )
                : e00723
                Affiliations
                [ 1 ] Division of Plastic, Reconstructive, Aesthetic and Hand Surgery Department of Surgery University Hospital of Basel Basel Switzerland
                [ 2 ] Division of Neuropathology Institute of Pathology University Hospital of Basel Basel Switzerland
                [ 3 ] Plastic and Reconstructive Surgery Department of Surgery, Oncology and Stomatology University of Palermo Palermo Italy
                [ 4 ] Division of Plastic and Reconstructive Surgery Department of Surgery Ghent University Hospital Gent Belgium
                Author notes
                [*] [* ] Correspondence

                Elisabeth A. Kappos, MD, Division of Plastic, Reconstructive, Aesthetic and Hand Surgery, Department of Surgery, University Hospital Basel, Basel, Switzerland.

                Email: Elisabeth.Kappos@ 123456usb.ch

                [†]

                Both authors contributed equally to this manuscript.

                Author information
                http://orcid.org/0000-0003-4057-1951
                Article
                BRB3723
                10.1002/brb3.723
                5516599
                28729931
                3aa82792-606b-4cb7-8c53-b60e949e6af2
                © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 May 2016
                : 15 November 2016
                : 22 March 2017
                Page count
                Figures: 2, Tables: 2, Pages: 12, Words: 10280
                Funding
                Funded by: Swiss National Science Foundation
                Award ID: 31003A_133076/1
                Funded by: Gottfried und Julia Bangerter‐Rhyner‐Stiftung
                Funded by: Department of Surgery, University Hospital of Basel
                Funded by: Nachwuchsförderungsfonds of the University of Basel
                Funded by: Freie Akademische Gesellschaft Basel
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                brb3723
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:19.07.2017

                Neurosciences
                automated gait analysis system,dynamic and static gait parameters,peripheral nerve regeneration,rat and mouse sciatic nerve

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