title: A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta).
abstract: The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies.
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Salegio
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bresnahan
authors.affiliation: 2 School of Engineering Science, Simon Fraser University , Surrey, British Columbia, Canada .
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Sparrey
authors.affiliation: 3 Taylor Collaboration, St. Mary's Medical Center , San Francisco, California.
authors.forename: William
authors.initials: W
authors.lastname: Camisa
authors.affiliation: 3 Taylor Collaboration, St. Mary's Medical Center , San Francisco, California.
authors.forename: Jason
authors.initials: J
authors.lastname: Fischer
authors.affiliation: 3 Taylor Collaboration, St. Mary's Medical Center , San Francisco, California.
authors.forename: Jeremi
authors.initials: J
authors.lastname: Leasure
authors.affiliation: 4 Department of Mechanical Engineering, University of Delaware , Newark, Delaware.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Buckley
authors.affiliation: 5 College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Fort Collins, Colorado.
authors.forename: Yvette S
authors.initials: YS
authors.lastname: Nout-Lomas
authors.affiliation: 6 Department of Neurosciences, University of California at San Diego , San Diego, California; Veterans Administration Medical Center, La Jolla, California.
authors.forename: Ephron S
authors.initials: ES
authors.lastname: Rosenzweig
authors.affiliation: 7 California National Primate Research Center, University of California at Davis , Davis, California.
authors.forename: Rod
authors.initials: R
authors.lastname: Moseanko
authors.affiliation: 7 California National Primate Research Center, University of California at Davis , Davis, California.
authors.forename: Sarah
authors.initials: S
authors.lastname: Strand
authors.affiliation: 7 California National Primate Research Center, University of California at Davis , Davis, California.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hawbecker
authors.affiliation: 7 California National Primate Research Center, University of California at Davis , Davis, California.
authors.forename: Marie-Josee
authors.initials: MJ
authors.lastname: Lemoy
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Jenny
authors.initials: J
authors.lastname: Haefeli
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Ma
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Nielson
authors.affiliation: 8 Departments of Physiological Science and Neurology, University of California at Los Angeles , Los Angeles, California.
authors.forename: V R
authors.initials: VR
authors.lastname: Edgerton
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Ferguson
authors.affiliation: 6 Department of Neurosciences, University of California at San Diego , San Diego, California; Veterans Administration Medical Center, La Jolla, California.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
authors.affiliation: 1 Department of Neurological Surgery, Brain and Spinal Injury Center, University of California at San Francisco , San Francisco, California.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Beattie
mesh_terms: D000818:Animals; D002574:Cervical Vertebrae; D003288:Contusions / Q000473:pathology* / Q000601:surgery; D004195:Disease Models, Animal; D008253:Macaca mulatta; D008297:Male; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000601:surgery
keywords: biomechanics of injury; contusion; functional recovery; primate; spinal cord injury