A controlled spinal cord contusion for the rhesus macaque monkey

Zhengwen Ma, Yi Ping Zhang, Wei Liu, Guofeng Yan, Yao Li, Lisa B E Shields, Melissa Walker, Kemin Chen, Wei Huang, Maiying Kong, Yi Lu, Benedikt Brommer, Xuejin Chen, Xiao-Ming Xu, Christopher B. Shields

Research output: Contribution to journalArticle

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Abstract

Most in vivo spinal cord injury (SCI) experimental models use rodents. Due to the anatomical and functional differences between rodents and humans, reliable large animal models, such as non-human primates, of SCI are critically needed to facilitate translation of laboratory discoveries to clinical applications. Here we report the establishment of a controlled spinal contusion model that produces severity-dependent functional and histological deficits in non-human primates. Six adult male rhesus macaque monkeys underwent mild to moderate contusive SCI using 1.0 and 1.5 mm tissue displacement injuries at T9 or sham laminectomy (n = 2/group). Multiple assessments including motor-evoked potential (MEP), somatosensory-evoked potential (SSEP), MR imaging, and monkey hindlimb score (MHS) were performed. Monkeys were sacrificed at 6 months post-injury, and the lesion area was examined for cavitation, axons, myelin, and astrocytic responses. The MHS demonstrated that both the 1.0 and 1.5 mm displacement injuries created discriminative neurological deficits which were severity-dependent. The MEP response rate was depressed after a 1.0 mm injury and was abolished after a 1.5 mm injury. The SSEP response rate was slightly decreased following both the 1.0 and 1.5 mm SCI. MRI imaging demonstrated an increase in T2 signal at the lesion site at 3 and 6 months, and diffusion tensor imaging (DTI) tractography showed interrupted fiber tracts at the lesion site at 4 h and at 6 months post-SCI. Histologically, severity-dependent spinal cord atrophy, axonal degeneration, and myelin loss were found after both injury severities. Notably, strong astrocytic gliosis was not observed at the lesion penumbra in the monkey. In summary, we describe the development of a clinically-relevant contusive SCI model that produces severity-dependent anatomical and functional deficits in non-human primates. Such a model may advance the translation of novel SCI repair strategies to the clinic.

Original languageEnglish (US)
Pages (from-to)261-273
Number of pages13
JournalExperimental Neurology
Volume279
DOIs
StatePublished - May 1 2016

Fingerprint

Macaca mulatta
Spinal Cord Injuries
Haplorhini
Wounds and Injuries
Primates
Motor Evoked Potentials
Somatosensory Evoked Potentials
Hindlimb
Myelin Sheath
Rodentia
Spinal Cord Regeneration
Diffusion Tensor Imaging
Gliosis
Laminectomy
Contusions
Atrophy
Axons
Spinal Cord
Theoretical Models
Animal Models

Keywords

  • Behavior assessments
  • Contusion
  • Electrophysiology
  • Monkey
  • Non-human primate
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Ma, Z., Zhang, Y. P., Liu, W., Yan, G., Li, Y., Shields, L. B. E., ... Shields, C. B. (2016). A controlled spinal cord contusion for the rhesus macaque monkey. Experimental Neurology, 279, 261-273. https://doi.org/10.1016/j.expneurol.2016.02.008

A controlled spinal cord contusion for the rhesus macaque monkey. / Ma, Zhengwen; Zhang, Yi Ping; Liu, Wei; Yan, Guofeng; Li, Yao; Shields, Lisa B E; Walker, Melissa; Chen, Kemin; Huang, Wei; Kong, Maiying; Lu, Yi; Brommer, Benedikt; Chen, Xuejin; Xu, Xiao-Ming; Shields, Christopher B.

In: Experimental Neurology, Vol. 279, 01.05.2016, p. 261-273.

Research output: Contribution to journalArticle

Ma, Z, Zhang, YP, Liu, W, Yan, G, Li, Y, Shields, LBE, Walker, M, Chen, K, Huang, W, Kong, M, Lu, Y, Brommer, B, Chen, X, Xu, X-M & Shields, CB 2016, 'A controlled spinal cord contusion for the rhesus macaque monkey', Experimental Neurology, vol. 279, pp. 261-273. https://doi.org/10.1016/j.expneurol.2016.02.008
Ma, Zhengwen ; Zhang, Yi Ping ; Liu, Wei ; Yan, Guofeng ; Li, Yao ; Shields, Lisa B E ; Walker, Melissa ; Chen, Kemin ; Huang, Wei ; Kong, Maiying ; Lu, Yi ; Brommer, Benedikt ; Chen, Xuejin ; Xu, Xiao-Ming ; Shields, Christopher B. / A controlled spinal cord contusion for the rhesus macaque monkey. In: Experimental Neurology. 2016 ; Vol. 279. pp. 261-273.
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