Modelling Neurological Diseases in Large Animals: Criteria for Model Selection and Clinical Assessment
Samantha L. Eaton,
Fraser Murdoch,
Nina M. Rzechorzek,
Gerard Thompson,
Claudia Hartley,
Benjamin Thomas Blacklock,
Chris Proudfoot,
Simon G. Lillico,
Peter Tennant,
Adrian Ritchie,
James Nixon,
Paul M. Brennan,
Stefano Guido,
Nadia L. Mitchell,
David N. Palmer,
C. Bruce A. Whitelaw,
Jonathan D. Cooper,
Thomas M. Wishart
Affiliations
Samantha L. Eaton
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Fraser Murdoch
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Nina M. Rzechorzek
Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
Gerard Thompson
Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
Claudia Hartley
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Benjamin Thomas Blacklock
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Chris Proudfoot
The Large Animal Research & Imaging Facility, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Simon G. Lillico
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Peter Tennant
The Large Animal Research & Imaging Facility, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Adrian Ritchie
The Large Animal Research & Imaging Facility, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
James Nixon
The Large Animal Research & Imaging Facility, Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Paul M. Brennan
Translational Neurosurgery, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
Stefano Guido
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Nadia L. Mitchell
Faculty of Agriculture and Life Sciences, Lincoln University, P.O. Box 85084, Lincoln 7647, New Zealand
David N. Palmer
Faculty of Agriculture and Life Sciences, Lincoln University, P.O. Box 85084, Lincoln 7647, New Zealand
C. Bruce A. Whitelaw
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Jonathan D. Cooper
Departments of Pediatrics, Genetics, and Neurology, Washington University School of Medicine in St. Louis, 660 S Euclid Ave, St. Louis, MO 63110, USA
Thomas M. Wishart
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK
Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models.