TY - JOUR
T1 - A unilateral cervical spinal cord contusion injury model in non-human primates (Macaca mulatta)
AU - Salegio, Ernesto A.
AU - Bresnahan, Jacqueline C.
AU - Sparrey, Carolyn J.
AU - Camisa, William
AU - Fischer, Jason
AU - Leasure, Jeremi
AU - Buckley, Jennifer
AU - Nout-Lomas, Yvette S.
AU - Rosenzweig, Ephron S.
AU - Moseanko, Rod
AU - Strand, Sarah
AU - Hawbecker, Stephanie
AU - Lemoy, Marie Josee
AU - Haefeli, Jenny
AU - Ma, Xiaokui
AU - Nielson, Jessica L.
AU - Edgerton, V. R.
AU - Ferguson, Adam R.
AU - Tuszynski, Mark H.
AU - Beattie, Michael S.
N1 - 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.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - biomechanics of injury
KW - contusion
KW - functional recovery
KW - primate
KW - spinal cord injury
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U2 - 10.1089/neu.2015.3956
DO - 10.1089/neu.2015.3956
M3 - Article
C2 - 26788611
AN - SCOPUS:84959208270
SN - 0897-7151
VL - 33
SP - 439
EP - 459
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 5
ER -