A unilateral cervical spinal cord contusion injury model in non-human primates (Macaca mulatta)

Ernesto A. Salegio, Jacqueline C. Bresnahan, Carolyn J. Sparrey, William Camisa, Jason Fischer, Jeremi Leasure, Jennifer Buckley, Yvette S. Nout-Lomas, Ephron S. Rosenzweig, Rod Moseanko, Sarah Strand, Stephanie Hawbecker, Marie Josee Lemoy, Jenny Haefeli, Xiaokui Ma, Jessica L. Nielson, V. R. Edgerton, Adam R. Ferguson, Mark H. Tuszynski, Michael S. Beattie

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)439-459
Number of pages21
JournalJournal of neurotrauma
Volume33
Issue number5
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the Veterans Administration, the Craig H. Neilsen Foundation (grants 190557, 260965 and 313739), the NIH (NS042291, NS067092, and NS079030), and the Wings for Life Foundation.

Publisher Copyright:
© Ernesto A. Salegio, et al., 2015; Published by Mary Ann Liebert, Inc. 2016.

Keywords

  • biomechanics of injury
  • contusion
  • functional recovery
  • primate
  • spinal cord injury

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